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140100.9576Molecular Surveillance of Multidrug-Resistant Bacteria among Refugees from Afghanistan in 2 US Military Hospitals during Operation Allies Refuge, 2021. In 2021, two US military hospitals, Landstuhl Regional Medical Center in Landstuhl, Germany, and Walter Reed National Military Medical Center (WRNMMC) in Bethesda, Maryland, USA, observed a high prevalence of multidrug-resistant bacteria among refugees evacuated from Afghanistan during Operation Allies Refuge. Multidrug-resistant isolates collected from 80 patients carried an array of antimicrobial resistance genes, including carbapenemases (bla(NDM-1), bla(NDM-5), and bla(OXA-23)) and 16S methyltransferases (rmtC and rmtF). Considering the rising transmission of antimicrobial resistance and unprecedented population displacement globally, these data are a reminder of the need for robust infection control measures and surveillance.202439530854
600410.9548Contact Lens Wear Alters Transcriptional Responses to Pseudomonas aeruginosa in Both the Corneal Epithelium and the Bacteria. PURPOSE: Healthy corneas resist colonization by virtually all microbes, yet contact lens wear can predispose the cornea to sight-threatening infection with Pseudomonas aeruginosa. Here, we explored how lens wear changes corneal epithelium transcriptional responses to P. aeruginosa and its impact on bacterial gene expression. METHODS: Male and female C57BL/6J mice were fitted with a contact lens on one eye for 24 hours. After lens removal, corneas were immediately challenged for 4 hours with P. aeruginosa. A separate group of naïve mice was similarly challenged with bacteria. Bacteria-challenged eyes were compared to uninoculated naïve controls, as was lens wear alone. Total RNA sequencing determined corneal epithelium and bacterial gene expression. RESULTS: Prior lens wear profoundly altered the corneal response to P. aeruginosa, including upregulated pattern recognition receptors (tlr3, nod1); downregulated lectin pathway of complement activation (masp1); amplified upregulation of tcf7, gpr55, ifi205, and wfdc2 (immune defense); and further suppression of efemp1 (corneal stromal integrity). Without lens wear, P. aeruginosa upregulated mitochondrial and ubiquinone metabolism genes. Lens wear alone upregulated axl, grn, tcf7, and gpr55 (immune defense) and downregulated Ca2+-dependent genes necab1, snx31, and npr3. P. aeruginosa exposure to prior lens wearing versus naïve corneas upregulated bacterial genes of virulence (popD), its regulation (rsmY, PA1226), and antimicrobial resistance (arnB, oprR). CONCLUSIONS: Prior lens wear impacts corneal epithelium gene expression, altering its responses to P. aeruginosa and how P. aeruginosa responds to it favoring virulence, survival, and adaptation. Impacted genes and associated networks provide avenues for research to better understand infection pathogenesis.202539932472
600320.9548Contact Lens Wear Alters Transcriptional Responses to Pseudomonas aeruginosa in Both the Corneal Epithelium and the Bacteria. PURPOSE: Healthy corneas resist colonization by virtually all microbes yet contact lens wear can predispose the cornea to sight-threatening infection with Pseudomonas aeruginosa. Here, we explored how lens wear changes corneal epithelium transcriptional responses to P. aeruginosa and its impact on bacterial gene expression. METHODS: Male and female C57BL/6J mice were fitted with a contact lens on one eye for 24 h. After lens removal, corneas were immediately challenged for 4 h with P. aeruginosa. A separate group of naïve mice were similarly challenged with bacteria. Bacteria-challenged eyes were compared to uninoculated naive controls as was lens wear alone. Total RNA-sequencing determined corneal epithelium and bacterial gene expression. RESULTS: Prior lens wear profoundly altered the corneal response to P. aeruginosa, including: upregulated pattern-recognition receptors (tlr3, nod1), downregulated lectin pathway of complement activation (masp1), amplified upregulation of tcf7, gpr55, ifi205, wfdc2 (immune defense) and further suppression of efemp1 (corneal stromal integrity). Without lens wear, P. aeruginosa upregulated mitochondrial and ubiquinone metabolism genes. Lens wear alone upregulated axl, grn, tcf7, gpr55 (immune defense) and downregulated Ca2(+)-dependent genes necab1, snx31 and npr3. P. aeruginosa exposure to prior lens wearing vs. naïve corneas upregulated bacterial genes of virulence (popD), its regulation (rsmY, PA1226) and antimicrobial resistance (arnB, oprR). CONCLUSION: Prior lens wear impacts corneal epithelium gene expression altering its responses to P. aeruginosa and how P. aeruginosa responds to it favoring virulence, survival and adaptation. Impacted genes and associated networks provide avenues for research to better understand infection pathogenesis.202439677621
815530.9540Gut bacteria enable prostate cancer growth. Testosterone-synthetizing gut bacteria drive resistance to therapy.202134618567
917240.9532These Are the Genes You're Looking For: Finding Host Resistance Genes. Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host-bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.202133004258
981150.9530"Infectious Supercarelessness" in Discussing Antibiotic-Resistant Bacteria. Many bacterial pathogens are exhibiting resistance to increasing numbers of antibiotics making it much more challenging to treat the infections caused by these microbes. In many reports in the media and perhaps even in discussions among physicians and biomedical scientists, these bacteria are frequently referred to as "bugs" with the prefix "super" appended. This terminology has a high potential to elicit unjustified inferences and fails to highlight the broader evolutionary context. Understanding the full range of biological and evolutionary factors that influence the spread and outcomes of infections is critical to formulating effective individual therapies and public health interventions. Therefore, more accurate terminology should be used to refer these multidrug-resistant bacteria.201628174759
816460.9524Antibiotic Resistance - A Cause for Reemergence of Infections. This article can rightly be called 'the rise of the microbial phoenix'; for, all the microbial infections whose doomsday was predicted with the discovery of antibiotics, have thumbed their noses at mankind and reemerged phoenix like. The hubris generated by Sir Alexander Fleming's discovery of Penicillin in 1928, exemplified best by the comment by William H Stewart, the US Surgeon General in 1967, "It is time to close the books on infectious diseases" has been replaced by the realisation that the threat of antibiotic resistance is, in the words of the Chief Medical Officer of England, Dame Sally Davies, "just as important and deadly as climate change and international terrorism". Antimicrobial resistance threatens to negate all the major medical advances of the last century because antimicrobial use is linked to many other fields like organ transplantation and cancer chemotherapy. Antibiotic resistance genes have been there since ancient times in response to naturally occurring antibiotics. Modern medicine has only driven further evolution of antimicrobial resistance by use, misuse, overuse and abuse of antibiotics. Resistant bacteria proliferate by natural selection when their drug sensitive comrades are removed by antibiotics. In this article the authors discuss the various causes of antimicrobial resistance and dwell in some detail on antibiotic resistance in gram-positive and gram-negative organisms. Finally they stress on the important role clinicians have in limiting the development and spread of antimicrobial resistance.202032026301
375170.9524Emerging mechanisms of antimicrobial resistance in bacteria and fungi: advances in the era of genomics. Bacteria and fungi continue to develop new ways to adapt and survive the lethal or biostatic effects of antimicrobials through myriad mechanisms. Novel antibiotic resistance genes such as lsa(C), erm(44), VCC-1, mcr-1, mcr-2, mcr-3, mcr-4, bla (KLUC-3) and bla (KLUC-4) were discovered through comparative genomics and further functional studies. As well, mutations in genes that hitherto were unknown to confer resistance to antimicrobials, such as trm, PP2C, rpsJ, HSC82, FKS2 and Rv2887, were shown by genomics and transcomplementation assays to mediate antimicrobial resistance in Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Saccharomyces cerevisae, Candida glabrata and Mycobacterium tuberculosis, respectively. Thus, genomics, transcriptomics and metagenomics, coupled with functional studies are the future of antimicrobial resistance research and novel drug discovery or design.201829319341
612780.9521Paenibacillus associated with milky disease in Central and South American scarabs. Thirty-one isolates of bacteria causing milky disease in scarab larvae collected in Central and South America were identified as Paenibacillus popilliae or Paenibacillus lentimorbus by use of DNA similarity analysis. The isolates were more similar to each other than to the North American isolates that are the type strains of the species. All of the bacteria of both species produced parasporal bodies, a characteristic previously believed to be unique to P. popilliae. Screening of the bacteria using PCR with parasporal protein primers revealed differences among the parasporal protein genes of P. popilliae isolates and between the parasporal genes of P. popilliae and P. lentimorbus. In contrast to P. popilliae from North America, none of the isolates from Central and South America was resistant to vancomycin, an indication of an interesting geographic distribution of the resistance genes.200011023744
665390.9520Making waves: How does the emergence of antimicrobial resistance affect policymaking? This article considers current trends in antimicrobial resistance (AMR) research and knowledge gaps relevant to policymaking in the water sector. Specifically, biological indicators of AMR (antibiotic-resistant bacteria and their resistance genes) and detection methods that have been used so far are identified and discussed, as well as the problems with and solutions to the collection of AMR data, sewage surveillance lessons from the COVID-19 pandemic, and the financial burden caused by AMR, which could be synergically used to improve advocacy on AMR issues in the water sector. Finally, this article proposes solutions to overcoming existing hurdles and shortening the time it will take to have an impact on policymaking and regulation in the sector.202134688095
3100.9520Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes named hemY, hemH, and hemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.201525646457
6609110.9519Antimicrobial-resistant bacteria in international travelers. PURPOSE OF REVIEW: Antimicrobial resistance (AMR) in bacteria poses a major risk to global public health, with many factors contributing to the observed increase in AMR. International travel is one recognized contributor. The purpose of this review is to summarize current knowledge regarding the acquisition, carriage and spread of AMR bacteria by international travelers. RECENT FINDINGS: Recent studies have highlighted that travel is an important risk factor for the acquisition of AMR bacteria, with approximately 30% of studied travelers returning with an acquired AMR bacterium. Epidemiological studies have shown there are three major risk factors for acquisition: travel destination, antimicrobial usage and travelers' diarrhea (TD). Analyses have begun to illustrate the AMR genes that are acquired and spread by travelers, risk factors for acquisition and carriage of AMR bacteria, and local transmission of imported AMR organisms. SUMMARY: International travel is a contributor to the acquisition and dissemination of AMR organisms globally. Efforts to reduce the burden of AMR organisms should include a focus on international travelers. Routine genomic surveillance would further elucidate the role of international travel in the global spread of AMR bacteria.202134267046
6689120.9519Wastewater-Based Epidemiology as a Complementary Tool for Antimicrobial Resistance Surveillance: Overcoming Barriers to Integration. This commentary highlights the potential of wastewater-based epidemiology (WBE) as a complementary tool for antimicrobial resistance (AMR) surveillance. WBE can support the early detection of resistance trends at the population level, including in underserved communities. However, several challenges remain, including technical variability, complexities in data interpretation, and regulatory gaps. An additional limitation is the uncertainty surrounding the origin of resistant bacteria and their genes in wastewater, which may derive not only from human sources but also from industrial, agricultural, or infrastructural contributors. Therefore, effective integration of WBE into public health systems will require standardized methods, sustained investment, and cross-sector collaboration. This could be achieved through joint monitoring initiatives that combine hospital wastewater data with agricultural and municipal surveillance to inform antibiotic stewardship policies. Overcoming these barriers could position WBE as an innovative tool for AMR monitoring, enhancing early warning systems and supporting more responsive, equitable, and preventive public health strategies.202540522150
8713130.9519Genomic Analysis of 18th-Century Kazakh Individuals and Their Oral Microbiome. The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome.202134943238
6667140.9518Antimicrobial resistance gene distribution: a socioeconomic and sociocultural perspective. The appearance of resistance to many first-line antimicrobial agents presents a critical challenge to the successful treatment of bacterial infections. Antimicrobial resistant bacteria and resistance genes are globally distributed, but significant variations in prevalence have been observed in different geographical regions. This article discusses possible relationships between socioeconomic and sociocultural factors and regional differences in the prevalence of antibiotic-resistant bacteria and their associated resistance genes. Findings indicate that the few studies that have been conducted to understand relationships between socioeconomic and sociocultural factors and antimicrobial resistance have focused on patterns of phenotypic antibiotic resistance. Yet, a critical need exists for molecular studies of human influences on bacterial resistance and adaptation. We propose that the results of these studies, coupled with well-coordinated culturally appropriate interventions that address specific socioeconomic and sociocultural needs may be necessary to reduce the scourge of antimicrobial resistance in both developing and developed countries.200820204098
6693150.9518Antimicrobial resistance among clinically significant bacteria in wildlife: An overlooked one health concern. Antimicrobial resistance (AMR) has emerged as a critical global health challenge. However, the significance of AMR is not limited to humans and domestic animals but extends to wildlife and the environment. Based on the analysis of > 200 peer-reviewed papers, this review provides comprehensive and current insights into the detection of clinically significant antimicrobial resistant bacteria and resistance genes in wild mammals, birds and reptiles worldwide. The review also examines the overlooked roles of wildlife in AMR emergence and transmission. In wildlife, AMR is potentially driven by anthropogenic activity, agricultural and environmental factors, and natural evolution. This review highlights the significance of AMR surveillance in wildlife, identifies species and geographical foci and gaps, and demonstrates the value of multifaceted One Health strategies if further escalation of AMR globally is to be curtailed.202438906487
2598160.9518The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq and Afghanistan in Germany. BACKGROUND: Multidrug-resistant bacteria represent a substantial global burden for human health, potentially fuelled by migration waves: in 2015, 476,649 refugees applied for asylum in Germany mostly as a result of the Syrian crisis. In Arabic countries, multiresistant bacteria cause significant problems for healthcare systems. Currently, no data exist describing antibiotic resistances in healthy refugees. Here, we assess the microbial landscape and presence of antibiotic resistance genes (ARGs) in refugees and German controls. To achieve this, a systematic study was conducted in 500 consecutive refugees, mainly from Syria, Iraq, and Afghanistan and 100 German controls. Stool samples were subjected to PCR-based quantification of 42 most relevant ARGs, 16S ribosomal RNA gene sequencing-based microbiota analysis, and culture-based validation of multidrug-resistant microorganisms. RESULTS: The fecal microbiota of refugees is substantially different from that of resident Germans. Three categories of resistance profiles were found: (i) ARGs independent of geographic origin of individuals comprising BIL/LAT/CMA, ErmB, and mefE; (ii) vanB with a high prevalence in Germany; and (iii) ARGs showing substantially increased prevalences in refugees comprising CTX-M group 1, SHV, vanC1, OXA-1, and QnrB. The majority of refugees carried five or more ARGs while the majority of German controls carried three or less ARGs, although the observed ARGs occurred independent of signatures of potential pathogens. CONCLUSIONS: Our results, for the first time, assess antibiotic resistance genes in refugees and demonstrate a substantially increased prevalence for most resistances compared to German controls. The antibiotic resistome in refugees may thus require particular attention in the healthcare system of host countries.201829458422
6668170.9518Complexities in understanding antimicrobial resistance across domesticated animal, human, and environmental systems. Antimicrobial resistance (AMR) is a significant threat to both human and animal health. The spread of AMR bacteria and genes across systems can occur through a myriad of pathways, both related and unrelated to agriculture, including via wastewater, soils, manure applications, direct exchange between humans and animals, and food exposure. Tracing origins and drivers of AMR bacteria and genes is challenging due to the array of contexts and the complexity of interactions overlapping health practice, microbiology, genetics, applied science and engineering, as well as social and human factors. Critically assessing the diverse and sometimes contradictory AMR literature is a valuable step in identifying tractable mitigation options to stem AMR spread. In this article we review research on the nonfoodborne spread of AMR, with a focus on domesticated animals and the environment and possible exposures to humans. Attention is especially placed on delineating possible sources and causes of AMR bacterial phenotypes, including underpinning the genetics important to human and animal health.201930924539
9108180.9517Learning from losers. Bacteria can overcome environmental challenges by killing nearby bacteria and incorporating their DNA.201729148975
4445190.9517Genomic Analysis and Resistance Mechanisms in Shigella flexneri 2a Strain 301. Shigella flexneri is one of the most prominent pathogenic bacteria in developing countries. In the battle against shigellosis and other bacterial diseases, antibiotic resistance has become an increasing global public health threat. Although the serious phenomenon of multidrug resistance (MDR) has been identified as one of the top three burdens on human health, resistance mechanisms are still poorly understood at the molecular level. In this study, we analyzed genomic data and the evolution of resistance in Shigella flexneri under sequential selection stress from three separate antibiotics: ciprofloxacin (CIP), ceftriaxone (CRO), and tetracycline. Through whole-genome sequencing, 82 chromosomal antibiotic resistance genes were identified. Re-sequencing of the evolved populations identified single nucleotide polymorphisms (SNPs) that contributed to MDR and SNPs that were specific to a single drug. A total of 40 SNPs in 8 genes and 3 intergenic regions, including mutations in metG (L582R) and 1538924, 1538924, and 1538924, appeared under each antibiotic. Several nonsynonymous mutations in gyrB (S464Y), ydgA (E378A), rob (R156H), and narX (K75E) were observed under selective pressure from CIP or CRO. Based on a bioinformatic analysis and previous reports, we discuss the contribution of these mutated genes to resistance. Therefore, more circumspect selection and use of antimicrobial drugs for treating shigellosis is necessary.201828853989