Spread Of Multidrug-resistant Research Articles

Epidemiological trends in serotypes distribution and antimicrobial resistance in Salmonella from humans in Taiwan, 2004-2022

ObjectivesSalmonella, a zoonotic pathogen, significantly impacts global human health. Understanding its serotype distribution and antimicrobial resistance is crucial for effective control measures and medical interventions. MethodsWe collected Salmonella isolates and demographic data from Taiwanese hospitals between 2004 and 2022, analyzing their serotypes and antimicrobial susceptibility. ResultsAmong 40,595 isolates, salmonellosis predominated in children aged 0-4 (61.2%) years and among males (55.2%). Males also showed higher rates of extraintestinal infections (18.1% vs 16.0%, P <0.001), particularly, in the ≥65 years age group (52.4%). The top five serovars were S. Enteritidis (32.8%), S. Typhimurium (21.7%), S. Newport (6.2%), S. Stanley (4.7%), and S. Anatum (4.0%). Notably, S. Enteritidis prevalence increased from 23.9% (2004-2005) to 43.6% (2021-2022). Antimicrobial resistance was high, with a 51.6% multidrug resistance (MDR) rate. Disturbingly, MDR rates exceeded 90% in serovars Albany, Schwarzengrund, Choleraesuis, and Goldcoast. Resistance to key therapeutic agents, azithromycin, cefotaxime, and ciprofloxacin, exhibited concerning upward trends, and the surge in cefotaxime and ciprofloxacin resistance was closely linked to the emergence and spread of MDR S. Anatum and S. Goldcoast clones. ConclusionsPrioritizing control measures against S. Enteritidis and closely monitoring the prevalence and spread of MDR clones are imperative to mitigate Salmonella infections in Taiwan.

Molecular detection of Klebsiella pneumoniae producing extended-spectrum beta-lactamase isolated from bat feces from the Tanjung Ringgit bat cave, Lombok Island, Indonesia

Background and Aim: Bats are a reservoir for the pathogenic bacteria Klebsiella pneumoniae and can spread it through feces that fall in nests/caves, carried, and dropped while they fly near human settlements, and from their saliva. The emergence and spread of multidrug resistance (MDR) strains of K. pneumoniae indicate that resistant to antibiotics, especially extended-spectrum beta-lactamase (ESBL), is considered an important global health threat. The aim of this study was to determine the presence of the gene encoding extended beta-lactamase in K. pneumoniae isolated from fresh bat feces collected from the Tanjung Ringgit bat cave, East Lombok. Materials and Methods: In this study, 150 fresh fecal samples were analyzed using standard microbiological techniques for the presence of K. pneumoniae. K. pneumoniae-positive isolates were subjected to antibiotic sensitivity testing, followed by molecular detection using polymerase chain reaction. Results: This study showed that 14 (9.3%) of 150 samples were positive for K. pneumoniae. Ten of the 14 samples (71.4%) were MDR isolates and 6 (42.9%) had the blaSHV gene identified. Conclusion: The presence of K. pneumoniae isolated from fresh bat feces, which is MDR and has the blaSHV gene encoding ESBL indicates that bats can be a reservoir for the transmission of MDR and ESBL bacteria has an impact on public health in the study area. Keywords: bat, blaSHV, extended-spectrum beta-lactamase, Klebsiella pneumoniae, public health.

Multidrug-resistant Stenotrophomonas maltophilia in residential aged care facilities: An emerging threat.

Stenotrophomonas maltophilia is a multidrug-resistant (MDR), Gram-negative bacterium intrinsically resistant to beta-lactams, including last-resort carbapenems. As an opportunistic pathogen, it can cause serious healthcare-related infections. This study assesses the prevalence, resistance profiles, and genetic diversity of S. maltophilia isolated from residential aged care facilities (RACFs). RACFs are known for their overuse and often inappropriate use of antibiotics, creating a strong selective environment that favors the development of bacterial resistance. The study was conducted on 73 S. maltophilia isolates recovered from wastewater and facility swab samples obtained from three RACFs and a retirement village. Phenotypic and genotypic assessments of the isolates revealed high carbapenem resistance, exemplifying their intrinsic beta-lactam resistance. Alarmingly, 49.3% (36/73) of the isolates were non-wild type for colistin, with minimum inhibitory concentration values of > 4 mg/L, and 11.0% (8/73) were resistant to trimethoprim-sulfamethoxazole. No resistance mechanisms were detected for either antimicrobial. Genotypic assessment of known lineages revealed isolates clustering with Sm17 and Sm18, lineages not previously reported in Australia, suggesting the potential ongoing spread of MDR S. maltophilia. Lastly, although only a few isolates were biocide tolerant (2.7%, 2/73), their ability to grow in high concentrations (64 mg/L) of triclosan is concerning, as it may be selecting for their survival and continued dissemination.

Abstract 5875: Upregulation of the RNA binding protein HuR by cancer-secreted exosome to mediate multidrug resistance

Abstract Background and Aim: Multidrug resistance (MDR) is an unresolved obstacle to cancer chemotherapy. It is usually caused by overexpression of drug efflux transporters including ABCG2. Exosomes are extracellular lipid vesicles released from all cells upon the fusion of multivesicular bodies with plasma membrane. Tumor-derived exosomes have been shown to mediate cell-to-cell transfer of oncogenic materials to promote drug resistance. Human antigen R (HuR) is an extensively studied RNA binding protein that regulates the stability, translation, and nucleus-to-cytoplasm shuttling of mRNAs. Numerous HuR-targeting mRNAs play crucial roles in tumorigenesis, invasion and metastasis. We have previously reported the induction of ABCG2 and MDR phenotype by HuR overexpression in colon cancer. HuR overexpression is linked with high-grade malignancy and poor prognosis in cancer patients. This study investigated the enrichment of HuR inducing microRNAs (miRNAs) in exosomes secreted from MDR colon cancer and its intracellular transfer to drive MDR. Method: Cancer exosome-mediated transfer of miRNAs from ABCG2-overexpressing resistant colon cancer cells S1M1-80 to a few sensitive colon cell lines was evaluated. Exosomes were isolated from S1M1-80 conditioned medium by differential centrifugation method. The uptake of fluorescence-labeled exosome from donor MDR cancer cells by recipient sensitive cells was visualized by fluorescence microscopy. MiRNA microarray was conducted to identify differentially expressed miRNAs in drug sensitive cells after incubation with S1M1-80-secreted exosomes. Western blot and qPCR analysis were conducted to measure HuR and ABCG2 expression. Result: Exosomes were isolated from resistant S1M1-80 cells, whose purity was confirmed by the presence of exosomal markers (Tsg101 and Alix) but absence of cellular marker (GRP78) by Western blot analysis. These exosomes reduced the apoptotic effect of SN-38 or 5-fluorouracil in sensitive colon cancer cell lines (HCT116, S1, and SW480) by inducing both HuR and ABCG2. A common upregulated miRNA (miR-155-5p) was identified by miRNA microarray in the sensitive cell lines after incubation with S1M1-80-derived exosomes. MiR-155-5p was found to induce HuR expression by promoting its translation. MiR-155-5p inhibitor was shown to reverse the upregulation of HuR in HCT116 cells after exosome incubation, which subsequently suppressed ABCG2 expression and the MDR phenotype. Furthermore, inhibition of exosome uptake by dynasore was found to prevent the induction of HuR/ABCG2, and re-sensitize the exosome-treated sensitive cells to SN38. Conclusion: MDR cells-derived exosomes may spread the drug resistance phenotype by transferring a miR-155-5p/HuR/ABCG2 regulatory machinery to sensitive cells. Inhibition of this exosomal transfer of regulatory materials may prevent the spread of MDR and sensitize cancer cells to chemotherapy. Citation Format: Kenneth K.W. To. Upregulation of the RNA binding protein HuR by cancer-secreted exosome to mediate multidrug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5875.

Sodium sulfite-driven Helicobacter pylori eradication: Unraveling oxygen dynamics through multi-omics investigation

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

2180. Pseudomonas aeruginosa epidemic high-risk clones and their association with multidrug-resistant

Abstract Background Pseudomonas aeruginosa (PAE) is an opportunistic pathogen associated with a variety of hospital infections. Treatment of infections caused by PAE is challenging due to the emergence of multidrug-resistant (MDR), which is associated with increased morbidity, mortality, and healthcare costs. Clonal spread and the presence of resistance genes probably explain the successful propagation of MDR. In Ecuador, data on the molecular epidemiology, as well as circulating clones, are limited. Therefore, the objective of this study is to know the population structure of PAE by identifying clones in clinical samples in Quito-Ecuador. Methods A significant set (45) of randomly selected clinical PAE isolates, including multidrug and non-multidrug resistant isolates, were assigned to sequence types (STs) and compared them with their antibiotic susceptibility profile. The genetic diversity was assessed by applying the multilocus sequence typing (MLST) scheme (Figure 1) and the genetic relationships between different STs were corroborated by the phylogenetic neighbor-net network (Figure 2).Figure 1.Analysis of the allelic profiles using eBURST algorithm.Figure 2.Splits Tree showing the distribution of all the sequence types obtained for the clinical Pseudomonas aeruginosa isolates studied. The Splits Tree was based on the analysis of the allelic profiles of the acsA, aroE, guaA, mutL, nuoD, ppsA and trpE genes. Asterisk mark (*) indicates the MDR isolates Results The analysis of seven loci, acsA, aroE, guaA, mutL, nuoD, ppsA and trpE, identified 24 different ST and the most prevalent STs were ST-3750 and ST-253. A SplitsTree was constructed with all the isolates analyzed. The majority of the MDR isolates were included in ST-3750 and ST-253, also 3 singleton ST was identified in to MDR isolates. The 20 different ST was found to non-MDR isolates, and only 3 ST were found in more the one isolates. Conclusion The population structure of clinical PAE presents in these isolates indicate a significant association between MDR isolates and the clonal types: all ST-3750 and ST-253 isolates were MDR. ST-3750 is closely related strains to the ST111 (CC111), and ST-253 and ST111 are a group of successful high-risk clones and widely distributed worldwide. The multiresistant-isolates studied are grouped in the most prevalent sequence types found, and the susceptible isolates correspond mainly to singleton sequence types. Therefore, these high-risk clones and their association with multidrug resistance phenotypes are contributing to the spread of MDR in Quito-Ecuador. Disclosures Jeannete Zurita, n/a, Pfizer: Grant/Research Support

Profile and resistance levels of 136 integron resistance genes

Integrons have played a major role in the rise and spread of multidrug resistance in Gram-negative pathogens and are nowadays commonplace among clinical isolates. These platforms capture, stockpile, and modulate the expression of more than 170 antimicrobial resistance cassettes (ARCs) against most clinically-relevant antibiotics. Despite their importance, our knowledge on their profile and resistance levels is patchy, because data is scattered in the literature, often reported in different genetic backgrounds and sometimes extrapolated from sequence similarity alone. Here we have generated a collection of 136 ARCs against 8 antibiotic families and disinfectants. Cassettes are cloned in a vector designed to mimic the genetic environment of a class 1 integron, and transformed in Escherichia coli. We have measured the minimal inhibitory concentration (MIC) to the most relevant molecules from each antibiotic family. With more than 500 MIC values, we provide an exhaustive and comparable quantitation of resistance conferred by ARCs. Our data confirm known resistance trends and profiles while revealing important differences among closely related genes. We have also detected genes that do not confer the expected resistance, to the point of challenging the role of the whole family of qac genes in resistance against disinfectants. Our work provides a detailed characterization of integron resistance genes at-a-glance.

Genomic epidemiology reveals multidrug resistant plasmid spread between Vibrio cholerae lineages in Yemen

Since 2016, Yemen has been experiencing the largest cholera outbreak in modern history. Multidrug resistance (MDR) emerged among Vibrio cholerae isolates from cholera patients in 2018. Here, to characterize circulating genotypes, we analysed 260 isolates sampled in Yemen between 2018 and 2019. Eighty-four percent of V. cholerae isolates were serogroup O1 belonging to the seventh pandemic El Tor (7PET) lineage, sub-lineage T13, whereas 16% were non-toxigenic, from divergent non-7PET lineages. Treatment of severe cholera with macrolides between 2016 and 2019 coincided with the emergence and dominance of T13 subclones carrying an incompatibility type C (IncC) plasmid harbouring an MDR pseudo-compound transposon. MDR plasmid detection also in endemic non-7PET V. cholerae lineages suggested genetic exchange with 7PET epidemic strains. Stable co-occurrence of the IncC plasmid with the SXT family of integrative and conjugative element in the 7PET background has major implications for cholera control, highlighting the importance of genomic epidemiological surveillance to limit MDR spread.

Whole-genome sequencing for One Health surveillance of antimicrobial resistance in conflict zones: a case study of Salmonella spp. and Campylobacter spp. in the West Bank, Palestine.

Antimicrobial resistance (AMR) is a critical global concern driven by the overuse, misuse, and/or usage of inadequate antibiotics on humans, animals' agriculture, and as a result of contaminated environments. This study is the first One Health survey in the Middle East that incorporated whole-genome sequencing (WGS) to examine the spread of AMR in Campylobacter spp. and Salmonella spp. This cross-sectional study was conducted to examine the role of AMR at the human-animal-environmental interface and was performed in Ramallah/Al-Bireh and Jerusalem governorates of the central West Bank, Palestine. In 2021 and 2022, a total of 592 samples were collected and analyzed. From a total of 65 Campylobacter jejuni and 19 Salmonella spp. isolates, DNA was extracted for WGS using Oxford Nanopore Technologies MinION platform. We found that the dominant serotypes of C. jejuni and Salmonella enterica were present in chicken manure, chicken meat sold in markets, and feces of asymptomatic farm workers, with high genetic similarities between the isolates regardless of origin. Additionally, our results showed rapid strain turnover in C. jejuni from the same sites between 2021 and 2022. Most of the positive Salmonella spp. samples were multidrug-resistant (MDR) S. enterica serovar Muenchen carrying the plasmid of emerging S. infantis (pESI) megaplasmid, conferring resistance to multiple antibiotics. Our findings highlight the spread of MDR foodborne pathogens from animals to humans through the food chain, emphasizing the importance of a One Health approach that considers the interconnections between human, animal, and environmental health. IMPORTANCE Prior to this study, there existed hardly an integrated human-animal-environmental study of Salmonellosis and Campylobacteriosis and related AMR in Middle Eastern countries. The few existing studies lack robust epidemiological study designs, adequate for a One Health approach, and did not use WGS to determine the circulating serotypes and their AMR profiles. Civil unrest and war in Middle Eastern countries drive AMR because of the breakdown of public health and food security services. This study samples simultaneously humans, animals, and the environment to comprehensively investigate foodborne pathogens in the broiler chicken production chain in Palestine using WGS. We show that identical serotypes of C. jejuni and S. enterica can be found in samples from chicken farms, chicken meat sold in markets, and asymptomatic broiler chicken production workers. The most striking feature is the rapid dynamic of change in the genetic profile of the detected species in the same sampling locations. The majority of positive Salmonella spp. samples are MDR S. enterica serovar Muenchen isolates carrying the pESI megaplasmid. The results demonstrate a close relationship between the S. enterica serovar Muenchen isolates found in our sample collection and those responsible for 40% of all clinical Salmonella spp. isolates in Israel as previously reported, with a sequence identity of over 99.9%. These findings suggest the transboundary spread of MDR S. enterica serovar Muenchen strains from animals to humans through the food chain. The study underscores the importance of combining integrated One Health studies with WGS for detecting environmental-animal-human transmission of foodborne pathogens that could not be detected otherwise. This study showcases the benefits of integrated environmental-animal-human sampling and WGS for monitoring AMR. Environmental samples, which may be more accessible in conflict-torn places where monitoring systems are limited and regulations are weak, can provide an effective AMR surveillance solution. WGS of bacterial isolates provides causal inference of the distribution and spread of bacterial serotypes and AMR in complex social-ecological systems. Consequently, our results point toward the expected benefits of operationalizing a One Health approach through closer cooperation of public and animal health and food safety authorities.

Spread of multidrug resistance in non-PCV13/PCV20 serotypes of Streptococcus pneumoniae: A cross-sectional study ten years after the introduction of pneumococcal conjugate vaccine in Japan

Ten years after the introduction of the pneumococcal conjugate vaccine (PCV) in Japan, the prevalence rates of non-PCV13 and non-PCV20 serotypes among pediatric pneumococcal isolates were 94.0% and 73.7%, respectively. The predominant non-PCV13/PCV20 serotypes (15A, 35B, and 23A) were mostly multidrug-resistant (≥80.5%), exhibiting non-susceptibility to penicillin.

Analysis of Regulatory Mechanism of AcrB and CpxR on Colistin Susceptibility Based on Transcriptome and Metabolome of Salmonella Typhimurium.

With the increasing and inappropriate use of colistin, the emerging colistin-resistant isolates have been frequently reported during the last few decades. Therefore, new potential targets and adjuvants to reverse colistin resistance are urgently needed. Our previous study has confirmed a marked increase of colistin susceptibility (16-fold compared to the wild-type Salmonella strain) of cpxR overexpression strain JSΔacrBΔcpxR::kan/pcpxR (simplified as JSΔΔ/pR). To searching for potential new drug targets, the transcriptome and metabolome analysis were carried out in this study. We found that the more susceptible strain JSΔΔ/pR displayed striking perturbations at both the transcriptomics and metabolomics levels. The virulence-related genes and colistin resistance-related genes (CRRGs) were significantly downregulated in JSΔΔ/pR. There were significant accumulation of citrate, α-ketoglutaric acid, and agmatine sulfate in JSΔΔ/pR, and exogenous supplement of them could synergistically enhance the bactericidal effect of colistin, indicating that these metabolites may serve as potential adjuvants for colistin therapy. Additionally, we also demonstrated that AcrB and CpxR could target the ATP and reactive oxygen species (ROS) generation, but not proton motive force (PMF) production pathway to potentiate antibacterial activity of colistin. Collectively, these findings have revealed several previously unknown mechanisms contributing to increased colistin susceptibility and identified potential targets and adjuvants for potentiating colistin treatment of Salmonella infections. IMPORTANCE Emergence of multidrug-resistant (MDR) Gram-negative (G-) bacteria have led to the reconsideration of colistin as the last-resort therapeutic option for health care-associated infections. Finding new drug targets and strategies against the spread of MDR G- bacteria are global challenges for the life sciences community and public health. In this paper, we demonstrated the more susceptibility strain JSΔΔ/pR displayed striking perturbations at both the transcriptomics and metabolomics levels and revealed several previously unknown regulatory mechanisms of AcrB and CpxR on the colistin susceptibility. Importantly, we found that exogenous supplement of citrate, α-ketoglutaric acid, and agmatine sulfate could synergistically enhance the bactericidal effect of colistin, indicating that these metabolites may serve as potential adjuvants for colistin therapy. These results provide a theoretical basis for finding potential new drug targets and adjuvants.

Spread of multidrug-resistant Pseudomonas aeruginosa in animal-derived foods in Beijing, China

Pseudomonas aeruginosa is the most common bacterium occurred in nosocomial infections and is also an important indicator of food spoilage. The worldwide spread of multidrug resistant (MDR) P. aeruginosa is threatening public health. However, the prevalence and spread of MDR P. aeruginosa through the food chain is little referred under the One Health perspective. Here, we collected a total of 259 animal-derived foods (168 chicken and 91 pork) from 16 supermarkets and farmer's markets in six regions of Beijing, China. The prevalence of P. aeruginosa in chicken and pork was 42.1 %. The phenotypic antimicrobial susceptibility testing showed that 69.7 % of isolates were MDR, and isolates from Chaoyang district exhibited a higher resistance rate compared to that from Xicheng district (p < 0.05). P. aeruginosa isolates exhibited high levels of resistance against β-lactams (91.7 %), cephalosporins (29.4 %), and carbapenems (22.9 %). Interestingly, none of strains showed resistance to amikacin. Whole-genome sequencing showed that all isolates carried various kinds of antimicrobial resistance genes (ARGs) and virulence genes (VGs), especially for blaOXA genes and phz genes. Multilocus sequence typing (MLST) analysis indicated that ST111 (12.8 %) was the most predominant ST. Notably, the emergence of ST697 clones in food-borne P. aeruginosa was firstly reported. In addition, the toxin pyocyanin was detected in 79.8 % of P. aeruginosa strains. These findings help to decipher the prevalence and the strong toxigenic ability of MDR P. aeruginosa from animal-derived foods and highlight the effective supervision of animal-derived food hygiene should be strengthened to prevent the spread of ARGs in a One Health strategy.

Mitigation of antimicrobial resistance genes in greywater treated at household level

Greywater often contains microorganisms carrying antimicrobial resistance genes (ARGs). Reuse of greywater thus potentially facilitates the enrichment and spread of multidrug resistance, posing a possible hazard for communities that use it. As water reuse becomes increasingly necessary, it is imperative to determine how greywater treatment impacts ARGs. In this study, we characterize ARG patterns in greywater microbial communities before and after treatment by a recirculating vertical flow constructed wetland (RVFCW). This greywater recycling method has been adopted by some small communities and households for greywater treatment; however, its ability to remove ARGs is unknown. We examined the taxonomic and ARG compositions of microbial communities in raw and treated greywater from five households using shotgun metagenomic sequencing. Total ARGs decreased in abundance and diversity in greywater treated by the RVFCW. In parallel, the microbial communities decreased in similarity in treated greywater. Potentially pathogenic bacteria associated with antimicrobial resistance and mobile genetic elements were detected in both raw and treated water, with a decreasing trend after treatment. This study indicates that RVFCW systems have the potential to mitigate antimicrobial resistance-related hazards when reusing treated greywater, but further measures need to be taken regarding persistent mobile ARGs and potential pathogens.

High-Efficiency Photodynamic Control of Antibiotic-Resistant Bacteria and Antibiotic-Resistant Genes in Wastewater Using Hydrogel-Decorated Porous Polyurethane Sponges with Metal Nanoparticles

The overuse and misuse of antibiotics in hospitals and other healthcare settings can lead to the development and spread of multidrug resistance (MDR) bacteria and water contaminants. In this study, silver nanoparticles (AgNPs)-loaded chitosan (CS)-alginate (AA) hydrogels were prepared to control wastewater MDR bacterial contaminants. CS-AA/AgNP composites strongly inhibited a wastewater MDR Enterobacter tabaci biofilm on membrane surfaces. The effect of AgNP-loaded CS-AA composite hydrogels on the gelation time, swelling ratio, in vitro degradation, and in vitro release properties was investigated. Furthermore, due to their outstanding environmentally friendly superhydrophobicity/superoleophilicity, sponges have proven compelling advantages in the area of water contaminants. Therefore, CS-AA/AgNP composites were coated on polyurethane sponges (PUSs) for disinfection applications in wastewater. CS-AA/AgNP composites and CS-AA/AgNP-coated (5 wt %) PUS exhibited higher photodynamic inactivation (PDI) of E. tabaci under blue LED light. In particular, modified PUS exhibited almost complete inactivation (5.1 log cfu/mL) at 40 min. Furthermore, tetracycline antibiotic degradation efficiency was observed to be 72.91% when the modified PUSs were added to antibiotic-polluted water in the designed reactor. In correlation with the degradation of resistance bacteria and antibiotics, the modified PUS in the designed reactor with PDI effect completely degraded tetracycline antibiotic resistance genes (ARGs) tetA and tetB at 45 min and 60 min, respectively. Specifically, PDI action on the modified PUS effectively degraded ARGs such as sul1, tetA, and tetB by 4.2, 3.2, and 2.9 log reduction (copies/mL), respectively. Excellent removal of ARGs after blue LED treatment indicated that the release of MDR pathogens and free ARGs was effectively controlled by the modified PUS photodynamic reaction. Therefore, the modified PUS can be considered as an alternative approach to remove MDR bacteria and free ARGs in the large-scale photodynamic disinfection process.

Repurposing prokaryotic clustered regularly interspaced short palindromic repeats-Cas adaptive immune system to combat antimicrobial resistance.

Despite achieving unparalleled progress in the field of science and technology, the global health community is still threatened by the looming pressure of infectious diseases. One of the greatest challenges is the rise in infections by antibiotic-resistant microorganisms. The misuse of antibiotics has led tothe present circumstances, and there isseemingly no solution. There is imminent pressure to develop new antibacterialtherapies to curb the rise and spread of multidrug resistance. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, having immense potential as a gene-editing tool, has gained considerable attention as an alternative antibacterialtherapy. Strategies, aiming toeither eliminatepathogenic strains or to restore sensitivity to antibiotics, are the main focus of research. This review deals with the development of CRISPR-Cas antimicrobials and theirdelivery challenges.

Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives.

The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.

Beta-lactamase production and conjugative ability of multidrug resistant Salmonella Typhi in Southern Benue, Nigeria

Objective: To examine multidrug resistant (MDR) Salmonella (S.) Typhi isolates obtained from the stool samples of patients attending secondary health centers in Southern Benue, Nigeria, for extended spectrum beta-lactamase (ESBL) production and conjugative ability. Methods: The double disc synergy test was used to screen for ESBL production in MDR isolates. The ability of S. Typhi to transfer resistance gene was determined by conjugation experiments using standard protocols, with slight modifications. Escherichia (E.) coli ATCC 25922 was used as the recipient organism. Result: The donor S. Typhi isolates showed resistance to all the classes of antibiotics except aminoglycosides and carbapenems. All isolates except TKP 106, APA 55, APA 78 and OGB 106 were positive for ESBL production. Reduction in the zones of inhibition of E. coli after incubation with S. Typhi showed evidence of conjugation and transfer of antibiotic resistance from S. Typhi to E. coli. Conclusions: The presence of ESBL-producing S. Typhi capable of conjugation poses a significant risk to the treatment and management of typhoid fever, which highlights the need for the regulation of antibiotic use through relevant policies and strategies that aim at halting the spread of MDR and ESBL-producing S. Typhi in such rural settings.

Biofilms preserve the transmissibility of a multi-drug resistance plasmid.

Self-transmissible multidrug resistance (MDR) plasmids are a major health concern because they can spread antibiotic resistance to pathogens. Even though most pathogens form biofilms, little is known about how MDR plasmids persist and evolve in biofilms. We hypothesize that (i) biofilms act as refugia of MDR plasmids by retaining them in the absence of antibiotics longer than well-mixed planktonic populations and that (ii) the evolutionary trajectories that account for the improvement of plasmid persistence over time differ between biofilms and planktonic populations. In this study, we evolved Acinetobacter baumannii with an MDR plasmid in biofilm and planktonic populations with and without antibiotic selection. In the absence of selection, biofilm populations were better able to maintain the MDR plasmid than planktonic populations. In planktonic populations, plasmid persistence improved rapidly but was accompanied by a loss of genes required for the horizontal transfer of plasmids. In contrast, in biofilms, most plasmids retained their transfer genes, but on average, plasmid, persistence improved less over time. Our results showed that biofilms can act as refugia of MDR plasmids and favor the horizontal mode of plasmid transfer, which has important implications for the spread of MDR.

Occurrence of antimicrobial resistance and antimicrobial resistance genes in methicillin-resistant Staphylococcus aureus isolated from healthy rabbits.

Methicillin-resistant globally, Staphylococcus aureus (MRSA) is a major cause of disease in both humans and animals. Several studies have documented the presence of MRSA in healthy and infected animals. However, there is less information on MRSA occurrence in exotic pets, especially healthy rabbits. This study aimed to look into the antimicrobial resistance profile, hidden antimicrobial-resistant genes in isolated bacteria, and to estimate prevalence of MRSA in healthy rabbits. Two-hundreds and eighteen samples, including 42 eyes, 44 ears, 44 oral, 44 ventral thoracic, and 44 perineal swabs, were taken from 44 healthy rabbits that visited the Prasu-Arthorn Animal Hospital, in Nakornpathom, Thailand, from January 2015 to March 2016. The traditional methods of Gram stain, mannitol fermentation, hemolysis on blood agar, catalase test, and coagulase production were used to confirm the presence of Staphylococcus aureus in all specimens. All bacterial isolates were determined by antimicrobial susceptibility test by the disk diffusion method. The polymerase chain reaction was used to identify the antimicrobial-resistant genes (blaZ, mecA, aacA-aphD, msrA, tetK, gyrA, grlA, and dfrG) in isolates of MRSA with a cefoxitin-resistant phenotype. From 218 specimens, 185 S. aureus were isolated, with the majority of these being found in the oral cavity (29.73%) and ventral thoracic area (22.7%), respectively. Forty-seven (25.41%) MRSAs were found in S. aureus isolates, with the majority of these being found in the perineum (16, 34.04%) and ventral thoracic area (13, 27.66%) specimens. Among MRSAs, 29 (61.7%) isolates were multidrug-resistant (MDR) strains. Most of MRSA isolates were resistant to penicillin (100%), followed by ceftriaxone (44.68%) and azithromycin (44.68%). In addition, these bacteria contained the most drug-resistance genes, blaZ (47.83%), followed by gyrA (36.17%) and tetK (23.4%). This study revealed that MRSA could be found even in healthy rabbits. Some MRSAs strains were MDR-MRSA, which means that when an infection occurs, the available antibiotics were not effective in treating it. To prevent the spread of MDR-MRSA from pets to owners, it may be helpful to educate owners about effective prevention and hygiene measures.

Prevalence of Urinary Tract Infection among Women in Arar, Saudi Arabia

Involuntary urination (IU) is recognized as a significant health problem. Urinary tract infection (UTI) can increase the risk of involuntary urination. Females are especially prone to UTIs for anatomical reasons. This study investigated the role of microbes in women suffering from UTIs and identified the causative bacteria and explored their antimicrobial resistance patterns that are of epidemiological importance regarding the spread of multi-drug resistance in Saudi Arabia. The study was conducted for a period of one year from September 2020 to August 2021. A total of 1027 midstream urine samples were collected in sterile containers from pregnant women of varied gestational ages attending antenatal clinics. Each sample was divided into two parts for urine analysis and microbial culture. It was found that the most effective antibiotic for the treatment of UTIs is norfloxacin (NOR) which was found to be 100% effective against all the bacterial isolates involved in UTIs. The second most effective antibiotic was found to be ofloxacin (Of) and proven as the effective antibiotic against the bacteria. The antibiotics amikacin (AMK), nitrofurantion (NI) and ampicillin (AMP) were found to be least effective for all UTI-causing bacteria. The singly isolated fungal species Candida albicans displayed sensitivity towards fluconazole.