The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem. - Related Documents




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439201.0000The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem. The airborne pathogen Mycobacterium tuberculosis is responsible for a present major public health problem worsened by the emergence of drug resistance. M. tuberculosis has acquired and developed streptomycin (STR) resistance mechanisms that have been maintained and transmitted in the population over the last decades. Indeed, STR resistant mutations are frequently identified across the main M. tuberculosis lineages that cause tuberculosis outbreaks worldwide. The spread of STR resistance is likely related to the low impact of the most frequent underlying mutations on the fitness of the bacteria. The withdrawal of STR from the first-line treatment of tuberculosis potentially lowered the importance of studying STR resistance. However, the prevalence of STR resistance remains very high, could be underestimated by current genotypic methods, and was found in outbreaks of multi-drug (MDR) and extensively drug (XDR) strains in different geographic regions. Therefore, the contribution of STR resistance to the problem of tuberculosis drug resistance should not be neglected. Here, we review the impact of STR resistance and detail well-known and novel candidate STR resistance mechanisms, genes, and mutations. In addition, we aim to provide insights into the possible role of STR resistance in the development of multi-drug resistant tuberculosis.202134946952
992210.9999De novo acquisition of antibiotic resistance in six species of bacteria. Bacteria can become resistant to antibiotics in two ways: by acquiring resistance genes through horizontal gene transfer and by de novo development of resistance upon exposure to non-lethal concentrations. The importance of the second process, de novo build-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying the de novo antibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole-genome sequencing at two time points of the evolutionary trajectory. In this study, we found that (1) all of the six strains can develop high levels of resistance against most antibiotics; (2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination; (3) the number of mutations varies widely, with Y. enterocolitica having by far the most; (4) in the case of fluoroquinolone resistance, a mutational pattern of gyrA combined with parC is conserved in five of six species; and (5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes. The outcome of this study may assist policymakers when formulating practical strategies to prevent development of antimicrobial resistance in human and veterinary health care.IMPORTANCEMost studies on de novo development of antimicrobial resistance have been performed on Escherichia coli. To examine whether the conclusions of this research can be applied to more bacterial species, six species of veterinary importance were made resistant to six antibiotics, each of a different class. The rapid build-up of resistance observed in all six species upon exposure to non-lethal concentrations of antimicrobials indicates a similar ability to adjust to the presence of antibiotics. The large differences in the number of DNA mutations accompanying de novo resistance suggest that the mechanisms and pathways involved may differ. Hence, very similar phenotypes can be the result of various genotypes. The implications of the outcome are to be considered by policymakers in the area of veterinary and human healthcare.202539907470
439620.9999Insights into the processes that drive the evolution of drug resistance in Mycobacterium tuberculosis. At present, the successful transmission of drug-resistant Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, in human populations, threatens tuberculosis control worldwide. Differently from many other bacteria, M. tuberculosis drug resistance is acquired mainly through mutations in specific drug resistance-associated genes. The panel of mutations is highly diverse, but depends on the affected gene and M. tuberculosis genetic background. The variety of genetic profiles observed in drug-resistant clinical isolates underlines different evolutionary trajectories towards multiple drug resistance, although some mutation patterns are prominent. This review discusses the intrinsic processes that may influence drug resistance evolution in M. tuberculosis, such as mutation rate, drug resistance-associated mutations, fitness cost, compensatory mutations and epistasis. This knowledge should help to better predict the risk of emergence of highly resistant M. tuberculosis strains and to develop new tools and strategies to limit the development and spread of MDR and XDR strains.201830344622
439130.9999'To be, or not to be'-The dilemma of 'silent' antimicrobial resistance genes in bacteria. Antimicrobial resistance is a serious threat to public health that dramatically undermines our ability to treat bacterial infections. Microorganisms exhibit resistance to different drug classes by acquiring resistance determinants through multiple mechanisms including horizontal gene transfer. The presence of drug resistance genotypes is mostly associated with corresponding phenotypic resistance against the particular antibiotic. However, bacterial communities harbouring silent antimicrobial resistance genes-genes whose presence is not associated with a corresponding resistant phenotype do exist. Under suitable conditions, the expression pattern of such genes often revert and regain resistance and could potentially lead to therapeutic failure. We often miss the presence of silent genes, since the current experimental paradigms are focused on resistant strains. Therefore, the knowledge on the prevalence, importance and mechanism of silent antibiotic resistance genes in bacterial pathogens are very limited. Silent genes, therefore, provide an additional level of complexity in the war against drug-resistant bacteria, reminding us that not only phenotypically resistant strains but also susceptible strains should be carefully investigated. In this review, we discuss the presence of silent antimicrobial resistance genes in bacteria, their relevance and their importance in public health.202235882476
432540.9999Research Updates of Plasmid-Mediated Aminoglycoside Resistance 16S rRNA Methyltransferase. With the wide spread of multidrug-resistant bacteria, a variety of aminoglycosides have been used in clinical practice as one of the effective options for antimicrobial combinations. However, in recent years, the emergence of high-level resistance against pan-aminoglycosides has worsened the status of antimicrobial resistance, so the production of 16S rRNA methyltransferase (16S-RMTase) should not be ignored as one of the most important resistance mechanisms. What is more, on account of transferable plasmids, the horizontal transfer of resistance genes between pathogens becomes easier and more widespread, which brings challenges to the treatment of infectious diseases and infection control of drug-resistant bacteria. In this review, we will make a presentation on the prevalence and genetic environment of 16S-RMTase encoding genes that lead to high-level resistance to aminoglycosides.202235884160
432650.9999Antibiotic resistance in oral/respiratory bacteria. In the last 20 years, changes in world technology have occurred which have allowed for the rapid transport of people, food, and goods. Unfortunately, antibiotic residues and antibiotic-resistant bacteria have been transported as well. Over the past 20 years, the rise in antibiotic-resistant gene carriage in virtually every species of bacteria, not just oral/respiratory bacteria, has been documented. In this review, the main mechanisms of resistance to the important antibiotics used for treatment of disease caused by oral/respiratory bacteria--including beta-lactams, tetracycline, and metronidazole--are discussed in detail. Mechanisms of resistance for macrolides, lincosamides, streptogramins, trimethoprim, sulfonamides, aminoglycosides, and chloramphenicol are also discussed, along with the possible role that mercury resistance may play in the bacterial ecology.19989825225
432060.9999The mobilome landscape of biocide-resistance in Brazilian ESKAPE isolates. The increasing frequency of antibiotic-resistant bacteria is a constant threat to global human health. Therefore, the pathogens of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter spp.) are among the most relevant causes of hospital infections responsible for millions of deaths every year. However, little has been explored about the danger of microorganisms resistant to biocides such as antiseptics and disinfectants. Widely used in domestic, industrial, and hospital environments, these substances reach the environment and can cause selective pressure for resistance genes and induce cross-resistance to antibiotics, further aggravating the problem. Therefore, it is necessary to use innovative and efficient strategies to monitor the spread of genes related to resistance to biocides. Whole genome sequencing and bioinformatics analysis aiming to search for sequences encoding resistance mechanisms are essential to help monitor and combat these pathogens. Thus, this work describes the construction of a bioinformatics tool that integrates different databases to identify gene sequences that may confer some resistance advantage about biocides. Furthermore, the tool analyzed all the genomes of Brazilian ESKAPE isolates deposited at NCBI and found a series of different genes related to resistance to benzalkonium chloride, chlorhexidine, and triclosan, which were the focus of this work. As a result, the presence of resistance genes was identified in different types of biological samples, environments, and hosts. Regarding mobile genetic elements (MGEs), around 52% of isolates containing genes related to resistance to these compounds had their genes identified in plasmids, and 48.7% in prophages. These data show that resistance to biocides can be a silent, underestimated danger spreading across different environments and, therefore, requires greater attention.202439028534
434070.9999Predicting antimicrobial susceptibility from the bacterial genome: A new paradigm for one health resistance monitoring. The laboratory identification of antibacterial resistance is a cornerstone of infectious disease medicine. In vitro antimicrobial susceptibility testing has long been based on the growth response of organisms in pure culture to a defined concentration of antimicrobial agents. By comparing individual isolates to wild-type susceptibility patterns, strains with acquired resistance can be identified. Acquired resistance can also be detected genetically. After many decades of research, the inventory of genes underlying antimicrobial resistance is well known for several pathogenic genera including zoonotic enteric organisms such as Salmonella and Campylobacter and continues to grow substantially for others. With the decline in costs for large scale DNA sequencing, it is now practicable to characterize bacteria using whole genome sequencing, including the carriage of resistance genes in individual microorganisms and those present in complex biological samples. With genomics, we can generate comprehensive, detailed information on the bacterium, the mechanisms of antibiotic resistance, clues to its source, and the nature of mobile DNA elements by which resistance spreads. These developments point to a new paradigm for antimicrobial resistance detection and tracking for both clinical and public health purposes.202133010049
433680.9999Antibiotic Resistance in Bacteria-A Review. A global problem of multi-drug resistance (MDR) among bacteria is the cause of hundreds of thousands of deaths every year. In response to the significant increase of MDR bacteria, legislative measures have widely been taken to limit or eliminate the use of antibiotics, including in the form of feed additives for livestock, but also in metaphylaxis and its treatment, which was the subject of EU Regulation in 2019/6. Numerous studies have documented that bacteria use both phenotypis and gentic strategies enabling a natural defence against antibiotics and the induction of mechanisms in increasing resistance to the used antibacterial chemicals. The mechanisms presented in this review developed by the bacteria have a significant impact on reducing the ability to combat bacterial infections in humans and animals. Moreover, the high prevalence of multi-resistant strains in the environment and the ease of transmission of drug-resistance genes between the different bacterial species including commensal flora and pathogenic like foodborne pathogens (E. coli, Campylobacter spp., Enterococcus spp., Salmonella spp., Listeria spp., Staphylococcus spp.) favor the rapid spread of multi-resistance among bacteria in humans and animals. Given the global threat posed by the widespread phenomenon of multi-drug resistance among bacteria which are dangerous for humans and animals, the subject of this study is the presentation of the mechanisms of resistance in most frequent bacteria called as "foodborne pathoges" isolated from human and animals. In order to present the significance of the global problem related to multi-drug resistance among selected pathogens, especially those danger to humans, the publication also presents statistical data on the percentage range of occurrence of drug resistance among selected bacteria in various regions of the world. In addition to the phenotypic characteristics of pathogen resistance, this review also presents detailed information on the detection of drug resistance genes for specific groups of antibiotics. It should be emphasized that the manuscript also presents the results of own research i.e., Campylobacter spp., E. coli or Enetrococcus spp. This subject and the presentation of data on the risks of drug resistance among bacteria will contribute to initiating research in implementing the prevention of drug resistance and the development of alternatives for antimicrobials methods of controlling bacteria.202236009947
431790.9999Development and spread of bacterial resistance to antimicrobial agents: an overview. Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The emergence and spread of multiply resistant organisms represent the convergence of a variety of factors that include mutations in common resistance genes that extend their spectrum of activity, the exchange of genetic information among microorganisms, the evolution of selective pressures in hospitals and communities that facilitate the development and spread of resistant organisms, the proliferation and spread of multiply resistant clones of bacteria, and the inability of some laboratory testing methods to detect emerging resistance phenotypes. Twenty years ago, bacteria that were resistant to antimicrobial agents were easy to detect in the laboratory because the concentration of drug required to inhibit their growth was usually quite high and distinctly different from that of susceptible strains. Newer mechanisms of resistance, however, often result in much more subtle shifts in bacterial population distributions. Perhaps the most difficult phenotypes to detect, as shown in several proficiency testing surveys, are decreased susceptibility to beta-lactams in pneumococci and decreased susceptibility to vancomycin in staphylococci. In summary, emerging resistance has required adaptations and modifications of laboratory diagnostic techniques, empiric anti-infective therapy for such diseases as bacterial meningitis, and infection control measures in health care facilities of all kinds. Judicious use is imperative if we are to preserve our arsenal of antimicrobial agents into the next decade.200111524705
4797100.9999Antibiotic resistance among clinically important gram-positive bacteria in the UK. The resistance of bacteria to antibiotics, particularly those used for first-line therapy, is an increasing cause for concern. In the UK, the prevalence of resistance to methicillin and mupirocin in Staphylococcus aureus, and to penicillin and macrolides in Streptococcus pneumoniae, appear to be increasing. There has also been an increase in the number of hospitals where glycopeptide-resistant enterococci are known to have been isolated. The increases in methicillin-resistant S. aureus and glycopeptide-resistant enterococci are due, in part, to the inter-hospital spread of epidemic strains. Although new quinolones and streptogramins with activity against Gram-positive bacteria (including strains resistant to currently available agents) are under development, there is no reason to believe that resistance to these agents will not emerge. The control of resistance in Gram-positive bacteria will require a multi-faceted approach, including continued and improved surveillance, a reduction in the unnecessary use of antibiotics, and the application of other strategies such as vaccination.19989777517
3829110.9998Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical Escherichia coli Isolates. The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents.IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages.201729089428
4480120.9998Anaerobic bacteria and antibiotics: What kind of unexpected resistance could I find in my laboratory tomorrow? The purpose of this article is to set out some important considerations on the main emerging antibiotic resistance patterns among anaerobic bacteria. The first point concerns the Bacteroides fragilis group and its resistance to the combination of β-lactam+β-lactamase inhibitor. When there is overproduction of cephalosporinase, it results in increased resistance to the β-lactams while maintaining susceptibility to β-lactams/β-lactamase inhibitor combinations. However, if another resistance mechanism is added, such as a loss of porin, resistances to β-lactam+β-lactamase inhibitor combinations may occur. The second point is resistance to metronidazole occurring due to nim genes. PCR detection of nim genes alone is not sufficient for predicting resistance to metronidazole; actual MIC determinations are required. Therefore, it can be assumed that other resistance mechanisms can also be involved. Although metronidazole resistance remains rare for the B. fragilis group, it has nevertheless been detected worldwide and also been observed spreading to other species. In some cases where there is only a decreased susceptibility, clinical failures may occur. The last point concerns resistance of Clostridium species to glycopeptides and lipopeptides. Low levels of resistance have been detected with these antibiotics. Van genes have been detected not only in clostridia but also in other species. In conclusion, antibiotic resistance involves different mechanisms and affects many anaerobic species and is spreading worldwide. This demonstrates the need to continue with antibiotic resistance testing and surveys in anaerobic bacteria.201020971200
4422130.9998Diversity among multidrug-resistant enterococci. Enterococci are associated with both community- and hospital-acquired infections. Even though they do not cause severe systemic inflammatory responses, such as septic shock, enterococci present a therapeutic challenge because of their resistance to a vast array of antimicrobial drugs, including cell-wall active agents, all commercially available aminoglycosides, penicillin and ampicillin, and vancomycin. The combination of the latter two occurs disproportionately in strains resistant to many other antimicrobial drugs. The propensity of enterococci to acquire resistance may relate to their ability to participate in various forms of conjugation, which can result in the spread of genes as part of conjugative transposons, pheromone-responsive plasmids, or broad host-range plasmids. Enterococcal hardiness likely adds to resistance by facilitating survival in the environment (and thus enhancing potential spread from person to person) of a multidrug-resistant clone. The combination of these attributes within the genus Enterococcus suggests that these bacteria and their resistance to antimicrobial drugs will continue to pose a challenge.19989452397
4393140.9998Mechanisms of Staphylococcus aureus Antibiotics Resistance Revealed by Adaptive Laboratory Evolution. Infection caused by drug-resistant Staphylococcus aureus is a serious public health and veterinary concern. Lack of a comprehensive understanding of the mechanisms underlying the emergence of drug-resistant strains, it makes S. aureus one of the most intractable pathogenic bacteria. To identify mutations that confer resistance to anti-S. aureus drugs, we established a laboratory-based adaptive evolution system and performed 10 rounds of evolution experiments against 15 clinically used antibiotics. We discovered a panel of known and novel resistance-associated sites after performing whole-genome sequencing. Furthermore, we found that the resistance evolved at distinct rates. For example, streptomycin, rifampicin, fusidic acid and novobiocin all developed significant resistance quickly in the second round of evolution. Intriguingly, the cross-resistance experiment reveals that nearly all drug-resistant strains have varying degrees of increased sensitivity to fusidic acid, pointing to a novel approach to battle AMR. In addition, the in silico docking analysis shows that the evolved mutants affect the interaction of rifampcin-rpoB, as well as the novobiocin-gyrB. Moreover, for the genes we got in the laboratory evolution, mutant genes of clinical isolates of human had significant differences from the environmental isolates and animal isolates. We believe that the strategy and data set in this research will be helpful for battling AMR issue of S. aureus, and adaptable to other pathogenic microbes.202539762552
4155150.9998Resistance to tetracycline, macrolide-lincosamide-streptogramin, trimethoprim, and sulfonamide drug classes. The discovery and use of antimicrobial agents in the last 50 yr has been one of medicine's greatest achievements. These agents have reduced morbidity and mortality of humans and animals and have directly contributed to human's increased life span. However, bacteria are becoming increasingly resistant to these agents by mutations, which alter existing bacterial proteins, and/or acquisition of new genes, which provide new proteins. The latter are often associated with mobile elements that can be exchanged quickly across bacterial populations and may carry multiple antibiotic genes for resistance. In some case, virulence factors are also found on these same mobile elements. There is mounting evidence that antimicrobial use in agriculture, both plant and animal, and for environmental purposes does influence the antimicrobial resistant development in bacteria important in humans and in reverse. In this article, we will examine the genes which confer resistance to tetracycline, macrolide-lincosamide-streptogramin (MLS), trimethoprim, and sulfonamide.200211936257
4794160.9998Resistance to antibiotics used in dermatological practice. The increased prevalence of bacterial resistance is one of the major problems of medicine today. Antibiotic resistance can be defined as the situation where the minimal inhibitory concentration is greater than the concentration obtainable in vivo. Resistance genes are easily transferred among bacteria, especially bacteria on skin and mucous membranes. In dermatological patients the most important resistance problems are found among staphylococci, Propionibacterium acnes and, to some extent, streptococci. Staphylococcus aureus strains have developed worldwide resistance to penicillin due to betalactamase production in > 90% of cases, and methicillin resistance is now a major problem with resistance levels of > 50% in certain areas of the world. These resistant strains are often multiresistant, and include resistance to erythromycin and tetracycline, with resistance to quinolone developing rapidly. Group A streptococci are still susceptible to penicillin, but increasing problems with erythromycin and tetracycline have been reported. After treatment with both systemic and oral antibiotics, P. acnes develops resistance in more than 50% of cases, and it is estimated that one in four acne patients harbours strains resistant to tetracycline, erythromycin, and clindamycin. To limit the development of antibiotic resistance, it is necessary to establish an antibiotic policy (prescription rules, reimbursement strategy, development of both national and local guidelines, and limitations on non-medical use). Clinicians also need access to rapid diagnostic methods, including resistance testing. This may provide further data for surveillance systems, reporting both antibiotic consumption and resistance levels. The involvement of clinical doctors in teaching and research in this area is probably the most important aspect, along with their involvement in the formulation of national and local guidelines. In the future we may consider it more important to ensure that future patients can be offered antibiotic treatment, rather than focusing on the patient presenting today.19989990406
4294170.9998Anaerobic infections: update on treatment considerations. Anaerobic bacteria are the predominant indigenous flora of humans and, as a result, play an important role in infections, some of which are serious with a high mortality rate. These opportunistic pathogens are frequently missed in cultures of clinical samples because of shortcomings in collection and transport procedures as well as lack of isolation and susceptibility testing of anaerobes in many clinical microbiology laboratories. Correlation of clinical failures with known antibacterial resistance of anaerobic bacteria is seldom possible. Changes in resistance over time, and the discovery and characterization of resistance determinants in anaerobic bacteria, has increased recognition of problems in empirical treatment and has even resulted in changes in treatment guidelines. This review discusses the role of anaerobic bacteria in the normal flora of humans, their involvement in different mixed infections, developments in antibacterial resistance of the most frequent anaerobic pathogens and possible new treatment options.201020426496
4754180.9998Enterococci and streptococci. Besides Staphylococcus aureus, other Gram-positive bacteria have become multidrug-resistant and cause therapeutic problems, particularly amongst hospitalised patients. The acquisition of vancomycin resistance by strains of Enterococcus faecium and Enterococcus faecalis is of particular concern and has resulted in treatment failures. Some of the infections caused by these bacteria do respond to treatment with new antibiotics that have been released in the last few years, however more options are required as not all enterococci are inherently susceptible and resistance is beginning to emerge amongst those that were susceptible. Resistance to commonly used antibiotics is also emerging in Streptococcus spp., particularly to the tetracyclines and macrolides. In both genera, multiresistant strains spread between patients and between hospitals. In the laboratory, these bacteria show considerable susceptibility to tigecycline, with little propensity to develop resistance, indicating that tigecycline could assume an important role in controlling infections caused by these Gram-positive bacteria.200717659211
4322190.9998Multi-Drug Resistance in Bacterial Genomes-A Comprehensive Bioinformatic Analysis. Antimicrobial resistance is presently one of the greatest threats to public health. The excessive and indiscriminate use of antibiotics imposes a continuous selective pressure that triggers the emergence of multi-drug resistance. We performed a large-scale analysis of closed bacterial genomes to identify multi-drug resistance considering the ResFinder antimicrobial classes. We found that more than 95% of the genomes harbor genes associated with resistance to disinfectants, glycopeptides, macrolides, and tetracyclines. On average, each genome encodes resistance to more than nine different classes of antimicrobial drugs. We found higher-than-expected co-occurrences of resistance genes in both plasmids and chromosomes for several classes of antibiotic resistance, including classes categorized as critical according to the World Health Organization (WHO). As a result of antibiotic-resistant priority pathogens, higher-than-expected co-occurrences appear in plasmids, increasing the potential for resistance dissemination. For the first time, co-occurrences of antibiotic resistance have been investigated for priority pathogens as defined by the WHO. For critically important pathogens, co-occurrences appear in plasmids, not in chromosomes, suggesting that the resistances may be epidemic and probably recent. These results hint at the need for new approaches to treating infections caused by critically important bacteria.202337511196