Different Classes Of Antibiotics Research Articles

Niosomal-Based Drug Delivery Platforms: A Promising Therapeutic Approach to Fight Staphylococcus aureus Drug Resistance

Staphylococcus aureus, a prominent bacterial pathogen, presents formidable medical challenges owing to its rapid development of resistance. The emergence of multidrug resistant (MDR) S. aureus strains has become a pressing concern for healthcare systems, driving researchers to explore novel therapeutic strategies for managing infections associated with this pathogen. In this pursuit, niosomal-based platforms have emerged as promising candidates to effectively target S. aureus and fight conventional antimicrobial resistance. Niosomes comprise a bilayer membrane formed by nonionic surfactants, which can encapsulate both hydrophilic and hydrophobic drugs. These nanoparticles are known as vesicular delivery systems and have many advantages, such as low cost, less toxicity, and more flexibility and stability. Moreover, niosomes, being an effective drug delivery system, can directly interact with the bacterial cell envelope, thereby enhancing the pharmacokinetic activities of drugs at infected sites. A niosome-based delivery system can effectively treat S. aureus infections by destroying the biofilm community, increasing intracellular targeting, and enhancing the antibacterial activity. The main mechanisms of action of niosomes against resistant S. aureus strains involve the ability to resist enzymatic degradation, controlled release profile, and targeted drug delivery, which can provide an effective dosage of antimicrobial agents at the site of actions. In addition, niosomes have the potential to transfer wide-spectrum materials from different classes of antibiotics to nonantibiotic antimicrobial agents, such as natural compounds, antimicrobial peptides, and metallic nanoparticles. The combination of polymeric materials in the structure of a niosomal formulation could improve their bioavailability, loading capacity, and therapeutic efficacy for different applications. Furthermore, niosomes could find application in photodynamic therapy, offering a promising alternative to conventional treatments for eradicating drug-resistant S. aureus isolates. Finally, niosomal nanocarriers can be developed for delivering the drugs to desired sites by different routes of administration and could be considered a powerful strategy for overcoming the therapeutic obstacles caused by MDR S. aureus.

Antibiotics and antibiotic-associated diarrhea: a real-world disproportionality study of the FDA adverse event reporting system from 2004 to 2022

Background Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications.Methods We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics.ResultsA total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64–1.51 and 0.42; 95%CI: 0.16–1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06–31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58–17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74–17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09–14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69–7.44). 91.35% of antibiotics have an onset time of less than four weeks.ConclusionsThere is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately.

Microbiome dynamics, antibiotic resistance gene patterns and spoilage-associated genomic potential in fresh anchovies stored in different conditions

Fresh fish is a highly perishable product and is easily spoiled by microbiological activity and chemical oxidation of lipids. However, microbial spoilage is the main factor linked with the rapid fish sensorial degradation due to the action of specific spoilage organisms (SSOs) that have the ability to dominate over other microorganisms and produce metabolites responsible for off-flavours.We explored the microbial dynamics in fresh anchovies stored in different packaging (air, modified atmosphere, under vacuum) and temperatures (0, 4 and 10 °C) using shotgun metagenomics, highlighting the selection of different microbial species according to the packaging type. Indeed, Pseudoalteromonas nigrifaciens, Psychrobacter cryohalolentis and Ps. immobilis, Pseudomonas deceptionensis and Vibrio splendidus have been identified as the main SSOs in aerobically stored anchovies, while Shewanella baltica, Photobacterium iliopiscarium, Ps. cryohalolentis and Ps. immobilis prevailed in VP and MAP. In addition, we identified the presence of spoilage-associated genes, leading to the potential production of biogenic amines and different off-flavors (H2S, TMA). In particular, the abundance of microbial genes leading to BA biosynthesis increased at higher storage temperature, while those related to H2S and TMA production were enriched in aerobically and VP packed anchovies, suggesting that MAP could be an effective strategy in delaying the production of these compounds. Finally, we provided evidence of the presence of a wide range of antibiotic resistance genes conferring resistance to different classes of antibiotic (β-lactams, tetracyclines, polymyxins, trimethoprims and phenicols) and highlighted that storage at higher temperature (4 and 10 °C) boosted the abundance of ARG-carrying taxa, especially in aerobically and MAP packed fish.

Co-occurrence of heavy metals and antibiotics resistance in bacteria isolated from metal-polluted soil.

The indiscriminate deposition of metal-containing substances into the environment contributes significantly to high concentrations of metals in the soil resulting in resistance to metals and consequentially to antibiotics by inherent microbes which may eventually spread to other pathogenic microbes thereby elevating disease burden due to antibiotic resistance. The study aimed at determining the co-occurrence of resistance of bacteria isolated from metal-contaminated soil to heavy metals and subsequently, antibiotics. Metal-tolerant bacteria were randomly isolated from top soils from a battery waste site using the pour plate method. Selected isolates were identified using biochemical tests, then, subjected to elevating supplemented concentrations of different metal salts at 100-500 μg/mL to determine the minimum inhibitory concentration. Isolates tolerant to minimum three metals up to 400 μg/mL were subjected to Sulfamethoxazole-trimethoprim (25 μg), Imipenem (10 μg), Amoxicillin (30 μg), Ciprofloxacin (10 μg) and Tigecycline (15 μg) and observations interpreted using the guiding principle of the Clinical and Laboratory Standards Institute. Metal concentrations in the soils exceeded permissible limits. In total, 16 isolates were selected and identified as Proteus sp. (1), Pseudomonas spp. (5), Enterobacter spp. (2), Klebsiella spp. (2), Escherichia spp. (3), Raoultella spp. (2) and Rahnella sp. (1). Thirteen (81.25 %) of all isolates showed multi-resistance to the metals and seven exhibited multidrug-resistance, with 4 (57.1 %) showing resistance to three different classes of antibiotics and 3 (42.9 %) showed resistance to four antibiotic classes. Heavy metal-tolerant bacteria isolated from this study possess co-selection potentials as they showed resistance to different metals and antibiotics classes which is a concern to public health.

Antibacterial Efficiency of Tanacetum vulgare Essential Oil against ESKAPE Pathogens and Synergisms with Antibiotics.

Medicinal plants with multiple targets of action have become one of the most promising solutions in the fight against multidrug-resistant (MDR) bacterial infections. Tanacetum vulgare (Tansy) is one of the medicinal plants with antibacterial qualities that deserve to be studied. Thus, this research takes a closer look at tansy extract's composition and antibacterial properties, aiming to highlight its potential against clinically relevant bacterial strains. In this respect, the antibacterial test was performed against several drug-resistant pathogenic strains, and we correlated them with the main isolated compounds, demonstrating the therapeutic properties of the extract. The essential oil was extracted via hydrodistillation, and its composition was characterized via gas chromatography. The main isolated compounds known for their antibacterial effects were α-Thujone, β-Thujone, Eucalyptol, Sabinene, Chrysanthenon, Camphor, Linalool oxide acetate, cis-Carveol, trans-Carveyl acetate, and Germacrene. The evaluation of the antibacterial activity was carried out using the Kirby-Bauer and binary microdilution methods on Gram-positive and Gram-negative MDR strains belonging to the ESKAPE group (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). Tansy essential oil showed MIC values ranging from 62.5 to 500 μg/mL against the tested strains. Synergistic activity with different classes of antibiotics (penicillins, cephalosporins, carbapenems, monobactams, aminoglycosides, and quinolones) has also been noted. The obtained results demonstrate that tansy essential oil represents a promising lead for developing new antimicrobials active against MDR alone or in combination with antibiotics.

Chemical shift assignments of the catalytic domain of Staphylococcus aureus LytM

S. aureus resistance to antibiotics has increased rapidly. MRSA strains can simultaneously be resistant to many different classes of antibiotics, including the so-called “last-resort” drugs. Resistance complicates treatment, increases mortality and substantially increases the cost of treatment. The need for new drugs against (multi)resistant S. aureus is high. M23B family peptidoglycan hydrolases, enzymes that can kill S. aureus by cleaving glycine-glycine peptide bonds in S. aureus cell wall are attractive targets for drug development because of their binding specificity and lytic activity. M23B enzymes lysostaphin, LytU and LytM have closely similar catalytic domain structures. They however differ in their lytic activities, which can arise from non-conserved residues in the catalytic groove and surrounding loops or differences in dynamics. We report here the near complete 1H/13C/15N resonance assignment of the catalytic domain of LytM, residues 185–316. The chemical shift data allow comparative structural and functional studies between the enzymes and is essential for understanding how these hydrolases degrade the cell wall.

Deciphering the genetics of antagonism and antimicrobial resistance in Bacillus velezensis HU-91 by whole genome analysis

Bacillus species are well reported plant growth promoting rhizobacteria which play an important role in improving soil fertility, nutrient recycling, and controlling phytopathogens. Their use as biocontrol agents is an ecofriendly strategy but being a rhizospheric community, they could harbor antimicrobial resistance genes. In current study, rhizobacteria were isolated from the mono cropped wheat. Ten out of 50 isolates showed antifungal activity against Fusarium spp., economically important pathogens of wheat. The strain HU-91 with highest antifungal activity showed the biochemical traits of lipopeptide production. It also resisted multiple antibiotics of different classes (index ≥ 0.2) and was categorized as multidrug resistant bacteria. The strain HU-91 was identified as Bacillus velezensis based on its 16S rRNA homology (99 %). Whole genome analysis of B. velezensis HU-91 revealed 76 contigs with a total length of 3,952,697 bp, GC content 46.3 %, and a total of 3912 genes. Functional classification of genome predicted genes involved in drug resistance, and antagonism. A detailed genome analysis identified CAZymes and 10 biosynthetic gene clusters involved in antagonism. Various antimicrobial resistance genes associated with the resistance to different antimicrobial classes such as β lactams, tetracyclines, aminoglycosides, fluoroquinolones, macrolides, sulfonamides, and lincosamides were also found in the genome of HU-91. Furthermore, HU-91 lacked plasmid but harbored a well-developed CRISPR Cas system. The underlying mechanisms involved in the antimicrobial resistance were depicted as intrinsic based on the genes encoding production of antibiotics degrading enzymes and efflux pumps. These findings depict that HU-91 adapts the intrinsic mechanisms of drug resistivity to tolerate environmental stress. The lack of plasmid and presence of CRISPR Cas system advocate its safety to be used as bioinoculant.

Raw Meat and Antibiotic Resistance: A Comprehensive Study on Prevalence of Pathogens in Food Animals

This review examines the use of antimicrobial agents in food animals and their impact on human health, particularly the emergence and spread of Antimicrobial Resistance (AMR). While antimicrobial agents are commonly used in food animal production to prevent and treat bacterial infections, overuse has been linked to AMR. Various strategies to reduce antimicrobial use in food animals, including vaccines, improved animal husbandry practices, and alternative therapies, are discussed. However, the review acknowledges the limitations of these strategies, such as cost-effectiveness and potential unintended consequences. Information on the percentage of antimicrobial use and resistance in food animals is provided for different classes of antibiotics. The percentages of use and resistance vary among these classes, with tetracyclines having the highest percentage of use and erythromycin and tylosin having the highest percentage of resistance. The review cites studies on the prevalence of antimicrobial resistance in food animals, including Escherichia coli isolates from broiler chickens in the UK and Egypt. The review highlights the need for a comprehensive approach to reducing antimicrobial use in food animals and controlling the spread of AMR, including implementing more effective regulatory policies, promoting responsible use of antimicrobial agents, and developing alternative therapies and management practices. Overall, the review emphasizes the importance of addressing the issue of AMR in food animals to preserve the effectiveness of antimicrobial agents for both animal and human health.

Bacterial Profile and their Antimicrobial Susceptibility Pattern in Pediatric Septicemia patients from Tertiary Care Hospital.

Background:
 Blood stream infection is a life-threatening infection, leading to increased morbidity and mortality in pediatric population. Antimicrobial drug resistance is a major therapeutic challenge and may result in treatment failure. Thus, this study aimed to assess the bacterial profile causing septicemia and their antimicrobial resistance pattern among pediatric population.
 Methods: 
 This reterospective study was conducted in pathology department of Hameed Latif Hospital, Lahore, over a period of two years, from 1st January 2021 to 31 December 2022. Blood samples were aseptically collected and were transferred into Bact/Alert blood culture bottle. After the detection of microbial growth by Bact/Alert 3D system, bacterial isolates were identified by standard microbiological procedures. Antimicrobial sensitivity pattern was determined by Modified Kirby-Bauer disc diffusion method on Mueller Hinton agar. Data was entered and analyzed by using Microsoft Excel 2010.
 Results:
 In our study, out of 1306 blood culture samples, 217(16.6%) were positive for bacterial growth. Among positive cases, Gram negative organisms were predominant isolates 181(83.4%), while Gram positive organisms were isolated in 36(16.6%) samples. Most common bacterial isolates were S. typhi (24%), A.baumanii (19%), P.aeruginosa (9%), while S.aureus and MRSA were 8% each. Highly resistant class of drugs for Gram-positive bacteria were found to be Aminopenicillin (69.1%) and Macrolides (68.6%), while Gram-negative organisms showed maximum resistance against Tetracycline (72.9%), Fluoroquinolones (62.1%) and Cephalosporins (61%).
 Conclusion:
 Bacterial isolates clinically suspected cases of septicemia were high. Majority of bacterial isolates showed maximum drug resistance against different classes of antibiotics. To prevent antibiotic resistance, strict regulation of antibiotic utilization and infection control programs should be implemented.

Characterization of pyridylpiperazine-based efflux pump inhibitors for Acinetobacter baumannii.

In Acinetobacter baumannii, multidrug efflux pumps belonging to the resistance-nodulation-division (RND) superfamily result in decreased antibiotic susceptibility. Improving the activity of current antibiotics via efflux pump inhibitors (EPIs) represents an attractive alternative approach to control this bacterium. Pyridylpiperazines (PyrPips) are a new class of EPIs that can effectively inhibit the Escherichia coli RND efflux pump AcrAB-TolC and boost the activity of several antibiotics. Here we have evaluated and characterized whether the PyrPip chemical family is also able to boost antibiotic activity through inhibition of the RND efflux pumps in A. baumannii. Comparative structural modelling and docking, structure-activity relationship studies alongside molecular genetic approaches were deployed to improve, characterize and validate PyrPips' target. We showed that two enhanced PyrPip EPIs are capable of rescuing the activity of different classes of antibiotics in A. baumannii. By expressing A. baumannii main efflux pumps (AdeB, AdeG and AdeJ) individually in E. coli recombinant strains, we could gain further insights about the EPIs' capacity to act upon each pump. Finally, we showed that PyrPip EPIs are mostly acting through AdeJ inhibition via interactions with two key charged residues, namely E959 and E963. Our work demonstrates that PyrPip EPIs are capable of inhibiting RND efflux pumps of A. baumannii, and thus may present a promising chemical scaffold for further development.

Effective treatment of a broad-host-range lytic phage SapYZU15 in eliminating Staphylococcus aureus from subcutaneous infection

Multidrug resistance (MDR) Staphylococcus aureus is frequently isolated from food products, and can cause severe clinical infection. Bacteriophage (phage) therapy is a promising biocontrol agent against MDR S. aureus in food contamination and clinical infections. In this study, the antimicrobial susceptibility of 47 S. aureus isolates from three swine farms, two slaughterhouses, and four markets (Yangzhou, China) were evaluated. The biological characteristics of four lytic S. aureus phages were compared and the lytic activity of phage SapYZU15 against MDR S. aureus was assessed using milk, fresh pork and a mouse model of subcutaneous abscess. The results showed that 28 S. aureus isolates (59.6%, 28/47) exhibited multiple antibiotic resistance to at least three different classes of antibiotics. Compared to SapYZU01, SapYZU02, and SapYZU03, SapYZU15 had a shorter latent period (10 min), larger burst size (322.00 PFU/cell), broader host range, wider temperature stability (−80 to 50 °C), and pH stability. Furthermore, SapYZU15 significantly reduces the counts of S. aureus in milk and pork (5.69 and 1.16 log colony-forming unit/mL, respectively) at 25 °C and controls the growth of S. aureus at 4 °C. Compared to the mice infected with S. aureus MRSA JCSC 4744 and cocktail (S. aureus YZUsa1, YZUsa4, YZUsa12, YZUsa14, and MRSA JCSC 4744), treatment with SapYZU15 led to faster tissue healing, less weight loss, and lower viable S. aureus counts in the murine abscess model. Moreover, prevention with SapYZU15 effectively inhibited abscess formation through a synergistic effect with pro-inflammatory cytokines. Consequently, our results suggest that SapYZU15 is an effective strategy for controlling S. aureus contamination in food products, and possesses an immense potential to treat and prevent clinic infection caused by MDR S. aureus strains. The interactions and mechanisms between SapYZU15 and its bacterial host differed depending on the model, temperature, and multiplicity of infection (MOI).

Therapeutic-oligonucleotides activated by nucleases (TOUCAN): A nanocarrier system for the specific delivery of clinical nucleoside analogues

Nucleoside analogues have been in clinical use since 1960s and they are still used as the first therapeutic option for several cancers and viral infections, due to their high therapeutic efficacy. However, their wide clinical acceptance has been limited due to their high toxicity and severe side effects to patients. Herein, we report on a nanocarrier system that delivers nucleosides analogues in a target-specific manner, making nucleoside-based therapeutics safer and with the possibility to be used in other human conditions. This system, named, Therapeutic OligonUCleotides Activated by Nucleases” (TOUCAN) combines: i) the recognition power of oligonucleotides as substrates, ii) the use of nucleases as enzymatic biomarkers and iii) the clinical efficacy of nucleoside analogues, in a single approach. As a proof-of-concept, we report on a TOUCAN that is activated by a specific nuclease produced by bacteria and releases a therapeutic nucleoside, floxuridine. We demonstrate, for the first time, that, by incorporating a therapeutic nucleoside analogue into oligonucleotide probes, we can specifically inhibit bacterial growth in cultures. In this study, Staphylococcus aureus was selected as the targeted bacteria and the TOUCAN strategy successfully inhibited its growth with minimal inhibitory concentration (MIC) values ranging from 0.62 to 40 mg/L across all tested strains. Moreover, our results indicate that the intravenous administration of TOUCANs at a dose of 20 mg/kg over a 24-h period is a highly effective method for treating bacterial infections in a mouse model of pyomyositis. Importantly, no signs of toxicity were observed in our in vitro and in vivo studies. This work can significantly impact the current management of bacterial infections, laying the grounds for the development of a different class of antibiotics. Furthermore, it can provide a safer delivery platform for clinical nucleoside therapeutics in any human conditions, such as cancer and viral infection, where specific nuclease activity has been reported.

Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

Surveillance of antimicrobial resistant Shiga toxin-producing E. coli O157:H7 in England, 2016-2020.

Shiga toxin-producing Escherichia coli (STEC) O157:H7 are zoonotic pathogens and transmission to humans occurs via contaminated food or contact with infected animals. The aim of this study was to describe the frequency, and distribution across the phylogeny, of antimicrobial resistance (AMR) determinants in STEC O157:H7 isolated from human cases in England. Short-read whole-genome sequencing data from 1473 isolates of STEC O157:H7 from all seven sub-lineages (Ia-Ic, IIa-IIc and I/II) were mapped to genes known to confer phenotypic resistance to 10 different classes of antibiotic. Long-read sequencing was used to determine the location and genomic architecture of the AMR determinants within phylogenetic clusters exhibiting multidrug resistance. Overall, 216/1473 (14.7%) isolates had at least one AMR determinant, although the proportion of isolates exhibiting AMR varied by sub-lineage. The highest proportion of AMR determinants were detected in sub-lineages Ib (28/64, 43.7%), I/II (18/51, 35.3%) and IIc (122/440, 27.7%). In all sub-lineages, the most commonly detected AMR determinants conferred resistance to the aminoglycosides, tetracyclines and sulphonamides, while AMR determinants conferring resistance to fluroquinolones, macrolides and third-generation cephalosporins were rarely detected. Long-read sequencing analysis showed that the AMR determinants were co-located on the chromosome in sub-lineages Ib and lineage I/II, whereas those associated with sub-lineage IIc were encoded on the chromosome and/or large plasmids. AMR genes were unevenly distributed across the different sub-lineages of STEC O157:H7 and between different clades within the same sub-lineage. Long-read sequencing facilitates tracking the transmission of AMR at the pathogen and mobile genetic element level.

Microbiological investigation of bacteria in raw eggs obtained from Obafemi Awolowo University, Nigeria

This study aimed to investigate the bacterial load and antibiotic susceptibility of bacteria isolated from uncooked eggs, with the goal of assessing potential health risks associated with their consumption. Six uncooked egg samples were collected, including samples from the eggshell, egg yolk, egg albumen, and their mixture. Bacterial enumeration was performed using the serial dilution and pour plate method on nutrient agar and MacConkey agar. Bacterial isolates were identified based on morphological and biochemical characteristics using Bergey's Manual of Determinative Bacteriology. Antibiotic susceptibility testing was conducted using the disc diffusion method on Mueller Hinton agar. The mean total bacterial load in the egg samples ranged from 3.6 x 10^4 to 5.0 x 104 CFU/ml, with coliforms ranging from 2.5 x 103 to 3.0 x 104 colony-forming unit per ml. A total of 48 isolates were obtained and identified, consisting of 13 Gram-negative and 35 Gram-positive bacteria. The identified bacteria exhibited varied susceptibility and resistance patterns to antibiotics. Gram-negative bacteria showed 100% susceptibility to gentamycin, ofloxacin, pefloxacin, and ciprofloxacin, except for Neisseria denitrificans, while demonstrating 100% resistance to nitrofurantoin, augmentin, and ceftriaxone. Most Gram-positive bacteria were susceptible to Pefloxacin and Streptomycin. Some isolates displayed resistance to multiple antibiotic classes, with Micrococcus varians and Bacillus laterosporus showing resistance to 6 and 7 different classes of antibiotics, respectively. The study findings emphasize the potential health risks associated with consuming uncooked eggs due to the presence of multiple antibiotic-resistant bacteria. These findings highlight the importance of proper cooking and handling practices for eggs to minimize the risk of foodborne infections caused by antibiotic-resistant bacteria. It underscores the need for awareness and implementation of appropriate food safety measures to safeguard public health.

The emergence of multi-drug resistant and virulence gene carrying Escherichia coli strains in the dairy environment: a rising threat to the environment, animal, and public health.

Escherichia coli is a common inhabitant of the intestinal microbiota and is responsible for udder infection in dairy cattle and gastro-urinary tract infections in humans. We isolated E. coli strains from a dairy farm environment in Xinjiang, China, and investigated their epidemiological characteristics, phenotypic and genotypic resistance to antimicrobials, virulence-associated genes, and phylogenetic relationship. A total of 209 samples were collected from different sources (feces, slurry, water, milk, soil) and cultured on differential and selective agar media (MAC and EMB). The presumptive identification was done by the VITEK2 system and confirmed by 16S rRNA gene amplification by PCR. Antimicrobial susceptibility testing was done by micro-dilution assay, and genomic characterization was done by simple and multiplex polymerase chain reaction (PCR). A total of 338 E. coli strains were identified from 141/209 (67.5%) of the samples. Most of the E. coli strains were resistant to sulfamethoxazole/trimethoprim (62.43%), followed by cefotaxime (44.08%), ampicillin (33.73%), ciprofloxacin (31.36%), tetracycline (28.99%), and a lesser extent to florfenicol (7.99%), gentamicin (4.44%), amikacin (1.77%), and fosfomycin (1.18%). All of the strains were susceptible to meropenem, tigecycline, and colistin sulfate. Among the resistant strains, 44.4% were identified as multi-drug resistant (MDR) showing resistance to at least one antibiotic from ≥3 classes of antibiotics. Eighteen out of 20 antibiotic-resistance genes (ARGs) were detected with sul2 (67.3%), blaTEM (56.3%), gyrA (73.6%), tet(B) (70.4%), aph(3)-I (85.7%), floR (44.4%), and fosA3 (100%, 1/1) being the predominant genes among different classes of antibiotics. Among the virulence-associated genes (VAGs), ompA was the most prevalent (86.69%) followed by ibeB (85.0%), traT (84.91%), ompT (73.96%), fyuA (23.1%), iroN (23.1%), and irp2 gene (21.9%). Most of the E. coli strains were classified under phylogenetic group B1 (75.45%), followed by A (18.34%), C (2.96%), D (1.18%), E (1.18%), and F (0.30%). The present study identified MDR E. coli strains carrying widely distributed ARGs and VAGs from the dairy environment. The findings suggested that the dairy farm environment may serve as a source of mastitis-causing pathogens in animals and horizontal transfer of antibiotic resistance and virulence genes carrying bacterial strains to humans via contaminated milk and meat, surface water and agricultural crops.

Tet-Dependent Gene Expression in Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is increasingly recognized as an important nosocomial pathogen among the Gram-negative bacteria. Intrinsic resistance to different classes of antibiotics makes treatment of infections challenging. A deeper understanding of S. maltophilia physiology and virulence requires molecular genetic tools. Here, we describe the implementation of tetracycline-dependent gene regulation (tet regulation) in this bacterium. The exploited tet regulatory sequence of transposon Tn10 contained the tetR gene and three intertwined promoters, one of which was required for regulated expression of a target gene or operon. The episomal tet architecture was tested with a gfp variant as a quantifiable reporter. Fluorescence intensity was directly correlated with the concentration of the inducer anhydrotetracycline (ATc) applied and the duration of induction. Also, the expression of the rmlBACD operon of S. maltophilia K279a was subjected to tet control. These genes code for the synthesis of dTDP-l-rhamnose, an activated nucleotide sugar precursor of lipopolysaccharide (LPS) formation. A ΔrmlBACD mutant was complemented with a plasmid carrying this operon downstream of the tet sequence. In the presence of ATc, the LPS pattern was similar to that of wild-type S. maltophilia, whereas without the inducer, fewer and apparently shorter O-antigen chains were detected. This underscores the functionality and usefulness of the tet system for gene regulation and, prospectively, the validation of targets for new anti-S. maltophilia drugs. IMPORTANCE Stenotrophomonas maltophilia is an emerging pathogen in hospital settings and poses a threat to immunocompromised patients. Due to a high level of resistance to different types of antibiotics, treatment options are limited. We here adapted a tool for inducible expression of genes of interest, known as the tet system, to S. maltophilia. Genes relevant to producing surface carbohydrate structures (lipopolysaccharide [LPS]) were placed under the control of the tet system. In the presence of an inducer, the LPS pattern was similar to that of wild-type S. maltophilia, whereas in the "off" state of the system (without inducer), fewer and apparently shorter versions of LPS were detected. The tet system is functional in S. maltophilia and may be helpful to reveal gene-function relationships to gain a deeper understanding of the bacterium's physiology and virulence.

Genotypic characteristics of Uropathogenic Escherichia coli isolated from complicated urinary tract infection (cUTI) and asymptomatic bacteriuria-a relational analysis.

Uropathogenic Escherichia coli (UPEC) is the predominant agent causing various categories of complicated urinary tract infections (cUTI). Although existing data reveals that UPEC harboured numerous virulence determinants to aid its survival in the urinary tract, the reason behind the occurrence of differences in the clinical severity of uninary tract infections (UTI) demonstrated by the UPEC infection is poorly understood. Therefore, the present study aims to determine the distribution of virulence determinants and antimicrobial resistance among different phylogroups of UPEC isolated from various clinical categories of cUTI and asymptomatic bacteriuria (ASB) E. coli isolates. The study will also attempt a relational analysis of the genotypic characteristics of cUTI UPEC and ASB E. coli isolates. A total of 141 UPEC isolates from cUTI and 160 ASB E. coli isolates were obtained from Universiti Malaya Medical Centre (UMMC). Phylogrouping and the occurrence of virulence genes were investigated using polymerase chain reaction (PCR). Antimicrobial susceptibility of the isolates to different classes of antibiotics was determined using the Kirby Bauer Disc Diffusion method. The cUTI isolates were distributed differentially among both Extraintestinal Pathogenic E. coli (ExPEC) and non-ExPEC phylogroups. Phylogroup B2 isolates were observed to possess the highest average aggregative virulence score (7.17), a probable representation of the capability to cause severe disease. Approximately 50% of the cUTI isolates tested in this study were multidrug resistant against common antibiotics used to treat UTI. Analysis of the occurrence of virulence genes among different cUTI categories demonstrated that UPEC isolates of pyelonephritis and urosepsis were highly virulent and had the highest average aggregative virulence scores of 7.80 and 6.89 respectively, compared to other clinical categories. Relational analysis of the occurrence of phylogroups and virulence determinants of UPEC and ASB E. coli isolates showed that 46.1% of UPEC and 34.3% of ASB E. coli from both categories were distributed in phylogroup B2 and had the highest average aggregative virulence score of 7.17 and 5.37, respectively. The data suggest that UPEC isolates which carry virulence genes from all four virulence genes groups studied (adhesions, iron uptake systems, toxins and capsule synthesis) and isolates from phylogroup B2 specifically could predispose to severe UTI involving the upper urinary tract. Therefore, specific analysis of the genotypic characteristics of UPEC could be further explored by incorporating the combination of virulence genes as a prognostic marker for predicting disease severity, in an attempt to propose a more evidence driven treatment decision-making for all UTI patients. This will go a long way in enhancing favourable therapeutic outcomes and reducing the antimicrobial resistance burden among UTI patients.

High burden of MDR, XDR, PDR, and MBL producing Gram negative bacteria causing infections in Kermanshah health centers during 2019-2020.

Microorganisms producing Metallo-Beta-Lactamase (MBL) are a threat and cause of concern as they have become one of the most feared resistance mechanisms. This study was designed to explore the prevalence of MBL production in clinical isolates of Gram negative bacteria using phenotypic MBL detection. A total of 248 isolates were collected from various clinical samples and were evaluated for carbapenem resistance and MBL production. All strains were screened for MBL production using Double Disk Confirmatory Test (DDCT). The results of screening for MBL production using phenotypic disk diffusion method showed that in the 85 isolates were carbapenemase positive; including, 10 (16.1%) Klebsiella pneumoniae, 9 (14.5%) Escherichia coli, 58 (93.6%) Acinetobacter baumannii, and 8 (12.9%) Pseudomonas aeruginosa isolates. Also, 83 (97.6) Carbapenemase-producing isolates were resistant to at least four classes of antimicrobials (MDR). A. baumannii was the most common carbapenem resistant bacterium in medical centers in Kermanshah. Significant multiple drug resistance (MDR) incidence was observed compared to different classes of antibiotics.

Down-Syndrome-Related Maternal Dysbiosis Might Be Triggered by Certain Classes of Antibiotics: A New Insight into the Possible Pathomechanisms

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations, the role of nutrients, vitamins, and, in general, the foodborne-associated background, as part of the events ultimately leading to chromosome nondisjunction, has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes. The possible association of DS development with maternal gut microbiota should therefore require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa; and hence, we might find associations between the use of the different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N = 30). By utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997–2020) and the estimated prevalence of people living with DS for the year 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.