Antibiotic Resistance Mechanisms Research Articles

2780. Factors associated with Staphylococcus aureus susceptibility to two lytic bacteriophages; Comparison of phage host susceptibility using a reference set of S. aureus

Abstract Background Timely access is a major concern when considering phage therapy. Using susceptible phage is critical for the outcomes of phage therapy. For timely access to susceptible phages, identifying factors associated with phage susceptibility and building a reference set (RS) to compare host ranges is needed. Methods Phage K, which was a well-documented lytic S. aureus phage, and phage PBSA02, which was a new S. aureus phage from the Korean phage biobank, were used. The efficiency of plating (EOP), the relative activity of phage against specific strain/host strain, and growth kinetics assays were used to determine phage susceptibility. The isolates with high lytic activity (HLA) were defined as susceptible (EOP > 1%). The phage PBSA02 and phage K susceptible groups were compared to the non-susceptible groups to determine the associating factors of phage susceptibility. Results We constructed a methicillin-resistant S. aureus (MRSA) RS using the Australian Group on Antimicrobial Resistance (AGAR) repository. We determined the predominant sequence types (ST) of MRSA in Australia in 2021; ST22 accounted for 90.1% of HA-MRSA and 5 STs for 67.9% of CA-MRSA (figure 1). Then, we randomly selected 39 AGAR MRSA isolates corresponding to each ST from each region in Australia (figure 1). Phage PBSA02 exhibited HLA against 56.4% of the 39 RS isolates, while phage K exhibited HLA against 30.8%. Phage PBSA02 showed HLA against 100% of ST93 and ST30 isolates following ST1 (62.5%), ST22 (37.5%), ST5 (20%) and ST45 (16.7%); phage K showed HLA against 100% of ST30 and 62.5% of ST22 isolates but against none of the ST93 isolates. Phage PBSA02 susceptibility correlated with the ST of MRSA isolates and ciprofloxacin susceptibility (table 1). Isolates from pneumonia/empyema tended to show phage PBSA02 susceptibility (table 1). Phage K susceptibility was also significantly associated with the ST (table 2). Conclusion Our study demonstrated that phage susceptibility was associated with the STs of MRSA, and the RS could be useful for a standardised comparison of the phage host range. Phage PBSA02 with broad susceptibility to the RS could be useful for phage therapy. Further work includes antibiotic synergy testing and resistance mechanism identification in these isolates. Disclosures All Authors: No reported disclosures

Metabolomics Method in Understanding and Sensitizing Carbapenem-Resistant Acinetobacter baumannii to Meropenem.

Carbapenem-resistant Acinetobacter baumannii (CRAB) strains are prevalent worldwide and represent a major threat to public health. However, treatment options for infections caused by CRAB are very limited as they are resistant to most of the commonly used antibiotics. Consequently, understanding the mechanisms underlying carbapenem resistance and restoring bacterial susceptibility to carbapenems hold immense importance. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate the metabolic mechanisms of antibiotic resistance in clinically isolated CRAB. Inactivation of the pyruvate cycle and purine metabolism is the most typical characteristic of CRAB. The CRAB exhibited a reduction in the activity of enzymes involved in the pyruvate cycle, proton motive force, and ATP levels. This decline in central carbon metabolism resulted in a decrease in the metabolic flux of the α-ketoglutarate-glutamate-glutamine pathway toward purine metabolism, ultimately leading to a decline in adenine nucleotide interconversion. Exogenous adenosine monophosphate (AMP) and adenosine triphosphate (ATP) enhance the killing efficacy of Meropenem against CRAB. The combination of ATP and Meropenem also has a synergistic effect on eliminating CRAB persisters and the biofilm, as well as protecting mice against peritonitis-sepsis. This study presents a novel therapeutic modality to treat infections caused by CRAB based on the metabolism reprogramming strategy.

Progress on mechanisms of antibiotic resistance in Clostridioides difficile.

Clostridioides difficile (CD) is one of the most common pathogens causing health-care-associated infectious diarrhea and is listed by the U.S. Centers for Disease Control and Prevention as an urgent antibiotic resistance (AR) threat. Many resistance genes can be transferred between different CD strains present in the clinical setting, community, and environment. The antimicrobial resistance (AMR) of CD continues to evolve with the emergence and acquisition of new drug resistance mechanisms. CD has developed diverse drug resistance mechanisms, such as drug alteration, modification of the target site, and extrusion of drugs via efflux pumps. Researches have provided comprehensive knowledge about resistance mechanisms of macrolides and quinolones in CD. However, the mechanisms of resistance for metronidazole, vancomycin, and other therapeutic antibiotics against Clostridioides difficile infection (CDI) are only beginning to be elucidated. Some previously unfound mechanisms, such as plasmid-mediated drug resistance in CD, may also play an important role. In this review, we summarize the research progress on drug resistance mechanisms of CD with antimicrobial drugs already used clinically, such as metronidazole, vancomycin, and fidaxomicin, thereby providing the references for the clinical treatment and prevention of CDI, as well as the development of new antibacterial drugs and detection kits for drug resistant bacteria.

Morphological Characterization of Calcium Carbonate Nanoparticles Derived from Blood Cockle Shells (Anadara granosa)

Blood cockle shells are a type of shellfish with distinctive bright red color that is commonly found in coastal areas of Asia, a rich source of protein, vitamins, and minerals, including calcium carbonate. Calcium carbonate (CaCO3) is a common mineral supplement that slowly paved its way into nano research to support bone health that also used in the treatment of bone infections due to its inherent properties; reduces inflammation, promotes bone healing, crucial role in the immune system, and slow degradability. The latest invention on CaCO3 from cockle shells, is an alternative mode of drug delivery to circumvent existing antibiotic resistance mechanisms and allow direct drug delivery to the target site, using locally sourced ingredients to reduce long-term high production costs. A top-down approach CaCO3 nanoparticles from blood cockle (Anadara granosa) shells were developed, known as calcium carbonate nanoparticles (CNPs). This research aims to characterize the morphology of CNPs from blood cockle shells via Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and Atomic Force Microscopy (AFM). A homogeneously spherical CNPs. with a mean diameter of 36.5 ± 2.3 nm was observed on TEM, so as FESEM. From AFM, the mean diameter for CNPs was 38.6 ± 3.6 nm The CNPs were spherical in shape, homogenously scattered, less agglomerate, porous with rough surfaces. The size and morphology of the CNPs from blood cockle shells were suitable for transport carrier in situ bone infection, according to the results.

Exogenous pyruvate promotes gentamicin uptake to kill antibiotic-resistant Vibrio alginolyticus

Elucidating antibiotic resistance mechanisms is necessary for developing novel therapeutic strategies. The increasing incidence of antibiotic-resistant Vibrio alginolyticus infection threatens both human health and aquaculture, but the mechanism has not been fully elucidated. Here, an isobaric tags for relative and absolute quantification (iTRAQ) functional proteomics analysis was performed on gentamicin-resistant V. alginolyticus (VA-RGEN) and a gentamicin-sensitive strain in order to characterize the global protein expression changes upon gentamicin resistance. Then, the bacterial killing assay and bacterial gentamicin pharmacokinetics were performed. Proteomics analysis demonstrated a global metabolic downshift in VA-RGEN, where the pyruvate cycle (the P cycle) was severely compromised. Exogenous pyruvate restored the P cycle activity, disrupting the redox state and increasing the membrane potential. It thereby potentiated gentamicin-mediated killing by approximately 3000- and 150-fold in vitro and in vivo, respectively. More importantly, bacterial gentamicin pharmacokinetics indicated that pyruvate enhanced gentamicin influx to a degree that exceeded the gentamicin expelled by the bacteria, increasing the intracellular gentamicin. Thus, our study suggests a metabolism-based approach to combating gentamicin-resistant V. algonolyticus, which paves the way for combating other types of antibiotic-resistant bacterial pathogens.

Mechanisms of total phosphorus removal and reduction of β-lactam antibiotic resistance genes by exogenous fungal combination activated sludge

This study utilized Trichoderma and activated sludge to construct combined activated sludge (TAS). The metagenomic approach was employed to examine the shifts in microbial community structure and function of TAS under amoxicillin stress and investigate the mechanism underlying the reduction of β-lactam antibiotic resistance genes (β-ARGs). The findings demonstrated that the elevated aundance of glpa, glpd, ugpq, glpq, and glpb were primarily responsible for the reduction in total phosphorus (TP) removal by TAS. The increased abundance of Proteobacteria and Verrucomicrobia led to enhanced expression of ugpb, phnd, and phne, thereby improving the TP removal of TAS. Furthermore, antibiotic inactivation has gradually become the primary antibiotic resistance mechanism in TAS. Specifically, an increase in the abundance of OXA-309 in TAS will decrease the probability of amoxicillin accumulation in TAS. A decrease in β-ARGs diversity confirmed this. This study presents a novel approach to reducing antibiotic and ARG accumulation in sludge.

Antibiotic therapy of acne and antibiotic resistance: State of the art

Acne is one of the most common dermatoses, with 117 million people diagnosed with the disease each year. Acne has a complex multifactorial genesis, including genetic predisposition and the influence of exposome factors. The direct mechanisms of the disease are associated with increased sensitivity of sebaceous glands to androgens, sebum hyperproduction, impaired keratinization at the mouth of hair follicles, and inflammation, in the induction of which Propionobacterium acnes is involved.
 The treatment of acne is complex, and one of its strategies is to regulate the number and activity of P. acnes through the use of antibacterial therapy. Antibacterial drugs have been used in the treatment of acne since the 1950s. They are included in a number of clinical guidelines and expert consensus documents for the treatment of the disease. However, the use of antibacterial drugs is limited by the formation of antibiotic resistance. Antibacterial drugs resistance in acne was first noted in the 1970s and was labeled as a global problem in the 2000s. The rapid increase in antibiotic resistance has prompted the development of strategies to prevent it and limit the use of antibacterial drugs in acne.
 This review presents information on the efficacy and place of antibacterial drugs in the treatment of acne, the epidemiology and mechanisms of antibiotic resistance, and strategies to overcome it. The authors consider and substantiate the effectiveness of a fixed combination of adapalene 0.1% and benzoyl peroxide 2.5%, based on the effect on the key links in the pathogenesis of acne, synergism of action and suppression of even antibiotic-resistant strains of P. acnes.

Sulfonium-Cross-Linked Hyaluronic Acid-Based Self-Healing Hydrogel: Stimuli-Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic-Resistant Bacteria.

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA-SS-HA-encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity reveals that HA-SS-HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics-encapsulated HA-SS-HA hydrogel can effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA can be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacteria.

Whole-transcriptome analysis after the acquisition of antibiotic resistance of Cronobacter sakazakii: Mechanisms of antibiotic resistance and virulence changes

The emergence of antibiotic-resistant bacteria led to the misuse of antibiotics, resulting in the emergence of more resistant bacteria and continuous improvement in their resistance ability. Cronobacter sakazakii (C. sakazakii) has been considered a pathogen that harms infants. Incidents of C. sakazakii contamination have continued globally, several studies have indicated that C. sakazakii is increasingly resistant to antibiotics. A few studies have explored the mechanism of antibiotic resistance in C. sakazakii, and some have examined the antibiotic resistance and changes in virulence levels. We aimed to investigate the antibiotic resistance mechanism and virulence differences in C. sakazakii. The level of virulence factors of C. sakazakii was modified after induction by antibiotics compared with the antibiotic-sensitive strains, and the XS001-Ofl group had the strongest capacity to produce enterotoxin (85.18 pg/mL) and hemolysin (1.47 ng/mL). The biofilm formation capacity after induction significantly improved. The number of bases and mapped reads in all groups accounted for more than 55 % and 70 %, as detected by transcriptomic analysis. The resistance mechanism of different antibiotics was more common in efflux pumps, cationic antimicrobial peptides, and biofilm formation pathways. The level of antibiotic resistance mainly affected the expression of virulence genes associated with flagella assembly and synthesis.

Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria.

Multidrug-resistant Gram-negative bacterial infections are exponentially increasing, posing one of the most urgent global healthcare and economic threats. Due to the lack of new therapies, the World Health Organization classified these bacterial species as priority pathogens in 2017, known as ESKAPE pathogens. This classification emphasizes the need for urgent research and development of novel targeted therapies. The majority of these priority pathogens are Gram-negative species, which possess a structurally dynamic cell envelope enabling them to resist multiple antibiotics, thereby leading to increased mortality rates. Despite 6 years having passed since the WHO classification, the progress in generating new treatment ideas has not been sufficient, and antimicrobial resistance continues to escalate, acting as a global ticking time bomb. Numerous efforts and strategies have been employed to combat the rising levels of antibiotic resistance by targeting specific resistance mechanisms. These mechanisms include antibiotic inactivating/modifying enzymes, outer membrane porin remodelling, enhanced efflux pump action, and alteration of antibiotic target sites. Some strategies have demonstrated clinical promise, such as the utilization of beta-lactamase inhibitors as antibiotic adjuvants, as well as recent advancements in machine-based learning employing artificial intelligence to facilitate the production of novel narrow-spectrum antibiotics. However, further research into an enhanced understanding of the precise mechanisms by which antibiotic resistance occurs, specifically tailored to each bacterial species, could pave the way for exploring narrow-spectrum targeted therapies. This review aims to introduce the key features of Gram-negative bacteria and their current treatment approaches, summarizing the major antibiotic resistance mechanisms with a focus on Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Additionally, potential directions for alternative therapies will be discussed, along with their relative modes of action, providing a future perspective and insight into the discipline of antimicrobial resistance.

Analysis of random mutations in Salmonella Gallinarum dihydropteroate synthase conferring sulfonamide resistance.

In bacteria and primitive eukaryotes, sulfonamide antibiotics block the folate pathway by inhibiting dihydropteroate synthase (FolP) that combines para-aminobenzoic acid (pABA) and dihydropterin pyrophosphate (DHPP) to form dihydropteroic acid (DHP), a precursor for tetrahydrofolate synthesis. However, the emergence of resistant strains has severely compromised the use of pABA mimetics as sulfonamide drugs. Salmonella enterica serovar Gallinarum (S. Gallinarum) is a significant source of antibiotic-resistant infections in poultry. Here, a sulfonamide-resistant FolP mutant library of S. Gallinarum was generated through random mutagenesis. Among resistant strains, substitution of amino acid Arginine 171 with Proline (R171P) in the FolP protein conferred the highest resistance against sulfonamide. Substitution of Phe28 with Leu or Ile (F28L/I) led to modest sulfonamide resistance. Structural modeling indicates that R171P and Phenylalanine 28 with leucine or isoleucine (F28L/I) substitution mutations are located far from the substrate-binding site and cause insignificant conformational changes in the FolP protein. Rather, in silico studies suggest that the mutations altered the stability of the protein, potentially resulting in sulfonamide resistance. Identification of specific mutations in FolP that confer resistance to sulfonamide would contribute to our understanding of the molecular mechanisms of antibiotic resistance.

A review on antibiotics in the environment, resistance in microbes, impact on human health and treatment and future strategies for tackling the global problem

The introduction of antibiotics was a blessing to human civilization as the antibiotics saved several million human and animal lives. Due to overuse and misuse of antibiotics by humans in the healthcare, and agriculture sectors, the residues of the antibiotics were reported in all the segments of the environment (surface water, groundwater, river water, soil, sediments, wastewater effluent, hospital effluent, livestock, fish, fruits, vegetables and milk) from ng to mg/L or kg that results in the rapid increase in the number of antibiotic resistant bacteria. Antibiotic resistance has been listed by the World Health Organization before Covid 19 as one of the top 10 threats to human health globally. Though antibiotic resistance is inevitable it is mainly anthropogenic and is an important factor of increased healthcare costs, longer hospital stay stress on hospital beds and ICU and higher rates of morbidity and mortality. The invention of new antibiotics to cope the resistant bacterial infection is the need of the hour but as bacterial infections is not an ongoing process (have a lower return) unlike chronic diseases hypertension, and diabetes the pharmaceutical companies are not very interested in the inventions. This article discusses the antibiotics in the different compartments of the environment, the antibacterial mechanisms of the antibiotics, causes of development and mechanisms of antibiotic resistance in bacteria and mechanisms/methods to combat antibiotic resistance.

Thiol-Based Modification of MarR Protein VnrR Regulates Resistance Toward Nitrofuran in Vibrio cholerae By Promoting the Expression of a Novel Nitroreductase VnrA and of NO-Detoxifying Enzyme HmpA.

Aims: Epidemiological investigations have indicated low resistance toward nitrofuran in clinical isolates, suggesting its potential application in the treatment of multidrug-resistant bacteria. Therefore, it is valuable to explore the mechanism of bacterial resistance to nitrofuran. Results: Through phenotypic screening of ten multiple antibiotic resistance regulator (MarR) proteins in Vibrio cholerae, we discovered that the regulator VnrR (VCA1058) plays a crucial role in defending against nitrofuran, specifically furazolidone (FZ). Our findings demonstrate that VnrR responds to FZ metabolites, such as hydroxylamine, methylglyoxal, hydrogen peroxide (H2O2), β-hydroxyethylhydrazine. Notably, VnrR exhibits reversible responses to the addition of H2O2 through three cysteine residues (Cys180, Cys223, Cys247), leading to the derepression of its upstream gene, vnrA (vca1057). Gene vnrA encodes a novel nitroreductase, which directly contributes to the degradation of FZ. Our study reveals that V. cholerae metabolizes FZ via the vnrR-vnrA system and achieves resistance to FZ with the assistance of the classical reactive oxygen/nitrogen species scavenging pathway. Innovation and Conclusion: This study represents a significant advancement in understanding the antibiotic resistance mechanisms of V. cholerae and other pathogens. Our findings demonstrate that the MarR family regulator, VnrR, responds to the FZ metabolite H2O2, facilitating the degradation and detoxification of this antibiotic in a thiol-dependent manner. These insights not only enrich our knowledge of antibiotic resistance but also provide new perspectives for the control and prevention of multidrug-resistant bacteria.

First Report of Plasmid-Mediated Macrolide-Clindamycin-Tetracycline Resistance in a High Virulent Isolate of Cutibacterium acnes ST115.

Cutibacterium acnes, a prevalent skin commensal, has emerged as a significant global challenge due to its widespread antibiotic resistance. To investigate the antibiotic resistance mechanisms and clinical characterization of C. acnes in Korea, we collected 22 clinical isolates from diverse patient specimens obtained from the National Culture Collection for Pathogens across Korea. Among the isolates, KB112 isolate was subjected to whole genome sequencing due to high resistance against clindamycin, erythromycin, tetracycline, doxycycline, and minocycline. The whole genome analysis of KB112 isolate revealed a circular chromosome of 2,534,481 base pair with an average G + C content of 60.2% with sequence type (ST) 115, harboring the potential virulent CAMP factor pore-forming toxin 2 (CAMP2), the multidrug resistance ABC transporter ATP-binding protein YknY, and the multidrug efflux protein YfmO. The genomic sequence also showed the existence of a plasmid (30,947 bp) containing the erm(50) and tet(W) gene, which confer resistance to macrolide-clindamycin and tetracycline, respectively. This study reports plasmid-mediated multi-drug resistance of C. acnes for the first time in Korea.

A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance.

The emergence and transmission of antibiotic resistance is a global public health crisis with significant burden on healthcare systems, resulting in high mortality and economic costs. In 2019, almost five million deaths were associated with drug-resistant infections, and if left unchecked, the global economy could lose $100 trillion by 2050. To effectively combat this crisis, it is essential for all countries to understand the current situation of antibiotic resistance. In this review, we examine the current driving factors leading to the crisis, impact of critical superbugs in three regions, and identify novel mechanisms of antibiotic resistance. It is crucial to monitor the phenotypic characteristics of drug-resistant pathogens and describe the mechanisms involved in preventing the emergence of cross-resistance to novel antimicrobials. Additionally, maintaining an active pipeline of new antibiotics is essential for fighting against diverse antibiotic-resistant pathogens. Developing antibacterial agents with novel mechanisms of action is a promising way to combat increasing antibiotic-resistant pathogens.

Nonadditive functional interactions between ligand-binding sites of the multidrug efflux pump AdeB from Acinetobacter baumannii.

Multidrug efflux is one of the major mechanisms of antibiotic resistance identified in clinical isolates of the human pathogen Acinetobacter baumannii. The multiple antibiotic resistance in this species is often enabled by the overproduction of the tripartite efflux pump AdeABC. In this pump, AdeB is the inner membrane transporter from the resistance-nodulation-division (RND) superfamily of proteins, which is responsible for the recognition and efflux of multiple structurally unrelated compounds. Like other RND transporters, AdeB is a trimeric protein with ligand-binding sites located in the large periplasmic domains. Previous structural studies, however, highlighted the uniqueness of AdeB interactions with ligands. Up to three ligand molecules were bound to one protomer of AdeB, mapping its substrate translocation path. In this study, we introduced single and double substitutions in the identified ligand-binding sites of AdeB. Our results show that the mechanism of substrate translocation by AdeB is different from that of other characterized RND transporters and that the functional interactions between the sites are nonadditive. We identified AdeB mutants with both the loss and the gain of antibiotic susceptibility phenotypes, as well as AdeB mutations making A. baumannii cells overproducing such pump variants even more susceptible to multiple antibiotics than efflux-deficient cells. IMPORTANCE Multidrug efflux pumps of the resistance-nodulation-division superfamily of proteins are important contributors to various aspects of bacterial physiology and antibiotic resistance. Studies of the best-characterized model transporter AcrB from Escherichia coli suggested that these transporters operate by a functional rotation mechanism in which various substrates bind to at least two different binding sites. This study suggests that the mechanism of AdeB is distinct and that the binding sites in this transporter are functionally linked.

Antibacterial and Toxic Activity of Geopropolis Extracts from Melipona subnitida (Ducke, 1910) (Hymenoptera: Apidae) and Scaptotrigona depilis (Moure, 1942) (Hymenoptera: Apidae).

Bacteria are associated with many infections that affect humans and present antibiotic resistance mechanisms, causing problems in health organisations and increased mortality rates. Therefore, it is necessary to find new antibacterial agents that can be used in the treatment of these microorganisms. Geopropolis is a natural product from stingless bees, formed by a mixture of plant resins, salivary secretions, wax and soil particles, the chemical composition of this natural product is diverse. Thus, this study aimed to evaluate antibacterial activity, antibiotic modulation and the toxicity of geopropolis extracts from the stingless bees, Melipona subnitida (Ducke, 1910) and Scaptotrigona depilis (Moure, 1942) against standard and multi-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacteria. Geopropolis samples were collected in a meliponary located in Camaragibe, Pernambuco, Brazil. To determine the Minimum Inhibitory Concentration (MIC) and antibiotic modulation we performed broth microdilution tests. Mortality tests were used to verify extract toxicity in the model Drosophila melanogaster. The microbiological tests showing that the M. subnitida extracts had better inhibitory effects compared to S. depilis, presenting direct antibacterial activity against standard and multi-resistant strains. The extracts potentialized antibiotic effects, suggesting possible synergy and did not present toxicity in the model used. The information obtained in this study highlights extracts as promising antibacterial agents and is the first study to evaluate bacterial activity in these extracts, in addition to verifying their modulating effects and determining toxicity in the model used.

A study on siderophore production and biofilm formation of klebsiella isolated from urine samples and detection of antibiotic resistance mechanisms

One of the most encountered infections by the physician in the community is Urinary tract infections, and over the years most of the pathogens responsible for the etiology have become resistant to antimicrobials. In nosocomial infections and immunocompromised individuals the most common pathogen implicated in UTI and catheter associated UTI are . are notorious for their antibiotic resistance and also cause systemic dissemination. A cross-sectional study that included 184 species isolated from urine samples collected from January 2020 – June 2021. Identification of isolates and speciation was done by biochemical reactions, antibiotic susceptibility pattern determined by Kirby Bauer disc diffusion method, virulence factors and antibiotic resistance mechanisms were detected by standard phenotypic methods. Among the patient’s female: male ratio was 1.7:1 and maximum number of cases were seen in the 21-30 age group.Maximum number of isolates belonged to (79.89%), followed by (20%). species showed maximum sensitivity to Imipenem, Meropenem, gentamicin, and amikacin. Out of the 184 isolates 22.86% were ESBL producers, 17.93% were AMP C producers and 9.24% were Carbapenamase producers. Among all isolates 94.56% were found to be biofilm producers, and all biofilm poducers were strongly associated with ESBL and Amp C production. Also 61.41% of total isolates were Siderophore producers. UTI is a predominant infection among younger age group females. High level of resistance to commonly used antibiotics were found, also the rising rate of antibiotic resistance mechanisms require further studies into the matter for ensuring better treatment success. Empirically amikacin and gentamicin could be used for treatment of UTI as they were found to be highly sensitive.

Modern concepts of antimicrobial therapy regimens for exacerbation of chronic obstructive pulmonary disease: A review

The publication discusses modern antimicrobial therapy regimens in patients with exacerbation of chronic obstructive pain. Lung diseases from the perspective of the updated version of national recommendations. Indications for prescribing antibiotics, etiological exacerbation risk factors, risk factors for encountering microorganisms with antibiotic resistance mechanisms, selection algorithm antimicrobial drug.

Unravelling the nsSNP mediated mechanism of antibiotic resistance in Salmonellaenterica serovar Typhi and identification of potential therapeutic alternatives: A genomics and structural bioinformatics study

Problem consideredTyphoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi) strains with multi-drug resistance (MDR) has become a significant global threat, as existing therapeutic options are limited. To combat this issue, efficient approaches are required to understand the resistance mechanism and identify potential therapeutic alternatives. MethodsIn this study, we employed concerted genomics and structural investigation to analyze single nucleotide polymorphisms (SNPs) in putative drug targets from whole genomes of Salmonella Typhi. The impact of these SNPs on the stability of encoded proteins and their effect on functional domains were analyzed to gain better insights into emerging MDR patterns. ResultsFrom the analysis of 360 putative drug target proteins in 60 whole genomes, we identified both prevalent and new mutations. Despite a relatively high conservation (>98 % identity) of protein targets and their functional domains in the MDR variants, INDEL mutations were found to induce local changes. The mutations were profiled as stabilizing or destabilizing based on their structural impact on the respective proteins. Interestingly, the MDR strains showed a preference for stabilizing mutations that altered local flexibility, thus compromising drug-susceptibility. ConclusionTo mitigate the risks associated with antibiotic stress-induced stabilizing mutations in drug targets, we performed virtual screening to identify over 500 potential phytocompounds. Through the screening process, Nimbolide emerged as a promising alternative anti-Typhoid candidate for future experimental validations due to its favourable pharmacokinetic properties, high target affinity (despite mutations), and greater interactive dynamics stability compared to conventional antibiotics.