Global Priority Pathogens Research Articles

The scourge of carbapenem resistant Enterobacteriaceae: how to fight back

The Enterobacteriaceae species cause both community acquired and health care associated infections like bloodstream infections, ventilator-associated pneumonia, intra-abdominal infections and urinary tract infections. Carbapenem-resistant Enterobacteriaceae (CRE) have been included in the list of global priority pathogens (GPP) declared by WHO in 2017. These infections pose a serious threat due to the associated significant morbidity and mortality. The mechanisms of antimicrobial resistance in these organisms are numerous; however, β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of these antibiotic-resistant strains on a global scale. The carbapenem resistance (CR) in Enterobacteriaceae has been recognized for the past two decades, but the carbapenemase-producing Enterobacteriaceae (CPE) has been a more recent issue and is spreading at an alarming pace worldwide. In this article, we conducted a systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases to identify relevant studies that reported the epidemiology and the outcomes for hospitalised patients with confirmed infections due to CRE and carbapenem-susceptible Enterobacteriaceae (CSE) published between 1 January 2010 and 30 August 2023.The results emphasize that patients with CRE infection still face a greater risk of mortality and need an urgent need for newer antibiotics and appropriate treatment regimens to reduce the risk of morbidity and mortality.

Colistin Resistance in WHO-Designated Global Priority Pathogens Isolated from Wastewater Effluents of Two Hospitals in Enugu Metropolis, South East Nigeria

Colistin Resistance in WHO-Designated Global Priority Pathogens Isolated from Wastewater Effluents of Two Hospitals in Enugu Metropolis, South East Nigeria

A systematic review on the WHO Global Priority Pathogens (GPP) List reported in animals, products, and by-products in Colombia

Background: The World Health Organization (WHO) published the Global Priority Pathogens (GPP) List for the Research and Development of Effective Antibiotics in 2017, a catalog of bacteria to be prioritized in the global fight against bacterial antibiotic resistance. Objective: To collect and app raise the scientific evidence on bacteria listed as GPP in animals and their products and by-products in Colombia, identifying knowledge gaps and providing finding-based recommendations. Materials and Methods: The review was carried out according to PRISMA guidelines. Only original articles published in peer35 reviewed journals were considered. Results: Twenty-one articles, published between 2001 and 2021, met the inclusion criteria. The geographical areas of study were the provinces of Antioquia, Cundinamarca —including Bogotá C.D., and Santander and Tolima. The main bacteria from the WHO´s list reported were fluoroquinolone-resistant Salmonella, methicillin-resistant and vancomycin-intermediate and resistant Staphylococcus aureus, and carbapenem-resistant ESBL-producing Enterobacteriaceae. The sources were feces, facilities, equipment, feed, animal drinking water, bed chip, tissues, and carcasses, related to broilers and laying hens, cattle, and pigs. Conclusions: Results obtained herein afford important advances in the knowledge of the phenomenon and its dynamic in Colombia. Nevertheless, much remains to be researched in the country, including standardized methods for the microbiological identification in veterinary medicine, as well as the evaluation of the antibiotic susceptibility patrons in bacteria in accordance with what is done in humans, among other aspects.

Novel drug candidates against antibiotic-resistant microorganisms: A review.

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus. Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.

Comparative genomics of carbapenem-resistant Pseudomonas aeruginosa strains sequence type 3151 isolated from two major hospitals in Hanoi, Vietnam

Carbapenem-resistant Pseudomonas aeruginosa belongs to the critical species of global priority pathogens, nevertheless, molecular mechanisms of such resistance in low- and middle-income countries are limited. In this context, we conducted a comparative genomic analysis between two clinical carbapenem-resistant P. aeruginosa strains VD641 and XP646 isolated from hospitals in Hanoi, Vietnam. The phenotypic-resistant profile revealed that both strains were resistant to at least 26 drugs belonging to 6 different antibiotic classes, and therefore they were identified as extensively drug-resistant bacteria. The chromosomal genome of strain VD641 was 7.1 Mb with GC a content of 65%, while the genome of XP646 consisted of an approximately 7.3 Mb with a GC content of 64.8%. The two strains belong to sequence type 3151 (ST3151). Genomic comparative analysis revealed that VD641 possessed higher numbers of antimicrobial resistance genes compared to XP646 (35 and 26 genes, respectively). This data was in accordance with their antibiotic-susceptibility profiles. Notably, the strain VD641 acquired a multidrug-resistant gene region with 223 kb in length carrying 11 antibiotic-resistant genes. Strains VD641 and XP646 acquired a blaIMP-15 and blaKPC-2 carbapenem-resistant gene, respectively. Analysis of virulent protein-protein interaction networks revealed six gene clusters involving the pathogenicity of the ST3151. Finally, four plasmids found in P. aeruginosa XP646 (n=1) and VD641 (n=3) carried different ARGs genes. The draft genomes and plasmid sequences of P. aeruginosa VD641 and XP646 were submitted to GenBank under BioSample accessions SAMN39268202 and SAMN39268203, respectively. The findings in our study underline that genomic surveillance is essential for management of carbapenem resistance emergence in healthcare setting in Vietnam.

Zoliflodacin: A hope to treat antibiotic-resistant Neisseria gonorrhoeae

Background: Neisseria gonorrhoeae is a gram negative diplococci which causess a sexually transmitted infection. N. gonorrhoeae is an obligate human pathogen that causes infection to the mucussecreting epithelial cells both in male and female. In 2017, the centre of disease control and World Health Organization published the list of global priority pathogens with denting therapeutic options, including antibiotic-resistant N. gonorrhoeae. During the covid-19 pandemic, excessive use of antibiotics led to raise of drug resistance. The infection is widespread and intractable. If this happens, more people will be left with an incurable infection which may cause serious health problems.
 Results: We characterized zoliflodacin thoroughly. Here is discussed the clinical trials and side effects on human health by searching different keywords like “zoliflodacin”, “covid-19”, “clinical trials” from different data sources like Pub-Med, Google-Scholar, and Science-Direct. Zoliflodacin targets antibiotic-resistant N. gonorrhoeae. Zoliflodacin is mainly known based on its therapeutic effects against N. gonorrhoeae. It acts by inhibiting bacterial type 2 topoisomerase with binding site in bacterial gyrase. Zoliflodacin is effective in treating gonococcal urogenital and rectal infection.
 Conclusion: Antibiotic is the only option to treat N. gonorrhoeae. There is no vaccine available to treat gonorrhea. The new drug, zoliflodacin, specifically targets antibiotic-resistant gonorrhea and its is why researchers have studied this antibiotic from different point of views. In this study, we elaborate the discovery of zoliflodacin, its mechanism of action, the current clinical trials, and the effectiveness of zoliflodacin.

Deterministic effect of oxygen level variation on shaping antibiotic resistome

An increase in acquisition of antibiotic resistance genes (ARGs) by pathogens under antibiotic selective pressure poses public health threats. Sub-inhibitory antibiotics induce bacteria to generate reactive oxygen species (ROS) dependent on dissolved oxygen (DO) levels, while molecular connection between ROS-mediated ARG emergence through DNA damage and metabolic changes remains elusive. Thus, the study investigates antibiotic resistome dynamics, microbiome shift, and pathogen distribution in hyperoxic (5–7 mg L−1), normoxic (2–4 mg L−1), and hypoxic (0.5–1 mg L−1) conditions using lab-scale bioreactor. Composite inoculums in the reactor were designed to represent comprehensive microbial community and AR profile from selected activated sludge. RT-qPCR and metagenomic analysis showed an increase in ARG count (100.98 ppm) with enrichment of multidrug efflux pumps (acrAB, mexAB) in hyperoxic condition. Conversely, total ARGs decreased (0.11 ppm) under hypoxic condition marked by a major decline in int1 abundance. Prevalence of global priority pathogens increased in hyperoxic (22.5%), compared to hypoxic (0.9%) wherein major decrease were observed in Pseudomonas, Shigella, and Borrelia. The study observed an increase in superoxide dismutase (sodA, sodB), DNA repair genes (nfo, polA, recA, recB), and ROS (10.4 µmol L−1) in adapted biomass with spiked antibiotics. This suggests oxidative damage that facilitates stress-induced mutagenesis providing evidence for observed hyperoxic enrichment of ARGs. Moreover, predominance of catalase (katE, katG) likely limit oxidative damage that deplete ARG breeding in hypoxic condition. The study proposes a link between oxygen levels and AR development that offers insights into mitigation and intervention of AR by controlling oxygen-related stress and strategic selection of bacterial communities.

Spectrum of World Health Organization global priority pathogens in hospitalized children - A single center experience

Objectives: To study the spectrum of World Health Organization (WHO) global priority pathogens in hospitalized children at our center. Material and Methods: This cross-sectional study was conducted between April 2021 to September 2022 in the Department of Pediatrics at Sri Aurobindo Institute of Medical Sciences and Post Graduate Institute (SAMC), Indore. All children admitted to the Pediatric and Adolescent Medicine Department; Ward, Pediatric Intensive Care Unit, Neonatal Intensive Care Unit, and Pediatric Surgical intensive Care Unit and with culture (Blood, urine, cerebrospinal fluid, and other body fluids/tissue) having grown at least one of the WHO priority pathogens, were studied. Results: In this study period, 100 children had positive cultures. We found that urine specimens had the most bacterial isolations 35 (35%), followed by blood 24 (24%). Escherichia coli was the most often isolated organism [25 (25%)], followed by Staphylococcus aureus [18 (18%)]. About 80% of E. coli and 70.59% of Klebsiella spp. were resistant to third-generation cephalosporins due to extended-spectrum beta-lactamase (ESBL), while 50% of S. aureus were Methicillin-resistant. In all, over half of the Enterobacteriaceae were resistant to carbapenem (49.21%) or third generation cephalosporins (55.56%) due to ESBL. Pseudomonas aeruginosa carbapenem resistance was found in 11.11% cases. Conclusion: In this study, WHO priority list pathogens, Enterobacteriaceae, methicillin-resistant S. aureus, Klebsiella species, and E. coli all show significant antimicrobial resistance (AMR). On the other hand, AMR trends for Acinetobacter baumanni, P. aeruginosa, and S. aureus (vancomycin resistant) are lower than the estimations provided by the WHO globally.

Combination drug strategies for biofilm eradication using synthetic and natural agents in KAPE pathogens.

Antibiotic resistance is a global threat caused by factors such as overuse of antibiotics, lack of awareness, development of biofilms etc. World Health Organization released a list of global priority pathogens which consisted of 12 species of bacteria categorized as expressing critical, high and medium resistance. Several Gram-negative and Gram-positive species are known to cause wide varieties of infections and have become multidrug or extremely drug resistant. Pathogens causing infections associated with invasive medical devices are biofilm producers and hence their treatment becomes difficult due to a structurally stable matrix which prevents antibiotics from penetrating the biofilm and thereby showing its effects. Factors contributing to tolerance are inhibition of penetration, restricted growth and activation of biofilm genes. Combination drug therapies has also shown potential to eradicate biofilm infections. A combination of inhaled Fosfomycin/tobramycin antibiotic strategy has been effective against Gram-negative as well as Gram positive organisms. Along with antibiotics, use of natural or synthetic adjuvants shows promising effects to treat biofilm infections. Fluroquinolone activity on biofilms is disrupted by low oxygen tension in the matrix, a strategy known as hyperbaric oxygen treatment that can enhance efficacy of antibiotics if well optimized. Adjuvants such as Ethylenediaminetetraacetic acid (EDTA), Sodium Dodecyl Sulphate (SDS) and chlorhexidine act by killing non-growing microbial cells aggregated on the inner layer of the biofilm. This review aims to list down current combination therapies used against Gram-negative and Gram-positive biofilm forming pathogens and brief about comparison of combination drugs and their efficacies.

Carbapenem Resistance in Gram-Negative Bacteria: A Hospital-Based Study in Egypt

Background and Objectives: The global spread of carbapenem resistance and the resulting increase in mortality forced the World Health Organization (WHO) to claim carbapenem-resistant enterobacteriaceae (CRE) as global priority pathogens. Our study aimed to determine the prevalence of carbapenemase-encoding genes and major plasmid incompatibility groups among Gram-negative hospital-based isolates in Egypt. Material and Methods: This cross-sectional study was carried out at Mansoura University Hospitals over 12 months, from January to December 2019. All the isolates were tested for carbapenem resistance. The selected isolates were screened by conventional polymerase chain reaction (PCR) for the presence of carbapenemase genes, namely blaKPC, blaIMP, blaVIM, and blaNDM-1. PCR-based plasmid replicon typing was performed using the commercial PBRT kit. Results: Out of 150 isolates, only 30 (20.0%) demonstrated carbapenem resistance. Klebsiella pneumoniae was the most resistant of all isolated bacteria, and blaNDM was the predominant carbapenemases gene, while the most prevalent plasmid replicons were the F replicon combination (FIA, FIB, and FII) and A/C. Plasmids were detected only in Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Pseudomonas aeruginosa. Remarkably, we found a statistically significant association between carbapenemase genes and plasmid replicons, including blaNDM, IncA/C, and IncX. Conclusions: Our study demonstrated an alarming rise of plasmid-mediated carbapenem-resistant bacteria in our locality. The coexistence of resistance genes and plasmids highlights the importance of a targeted antibiotic surveillance program and the development of alternative therapeutic options at the local and international levels. Based on our results, we suggest a large-scale study with more Enterobacteriaceae isolates, testing other carbapenemase-encoding genes, and comparing the replicon typing method with other plasmid detection methods. We also recommend a national action plan to control the irrational use of antibiotics in Egypt.

Development of diagnostic tests for pathogen identification and detection of antimicrobial resistance on WHO global priority pathogens using modular real-time nucleic acid amplification test.

Concerns regarding antimicrobial resistance (AMR) have resulted in the World Health Organization (WHO) designating so-called global priority pathogens (GPPs). However, little discussion has focused on the diagnosis of GPPs. To enable the simultaneous identification of pathogens and AMR, we developed a modular real-time nucleic acid amplification test (MRT-NAAT). Sequence-specific primers for each modular unit for MRT-NAAT pathogen identification and AMR sets were designed. The composition of the reaction mixture and the real-time PCR program were unified irrespective of primer type so to give MRT-NAAT modularity. Standard strains and clinical isolates were used to evaluate the performance of MRT-NAAT by real-time PCR and melting curve analysis. Probit analysis for the MRT-NAAT pathogen identification set was used to assess the limit of detection (LoD). The MRT-NAAT pathogen identification set was made up of 15 modular units 109-199bp in product size and with a Tms of 75.5-87.5°C. The LoD was < 15.548fg/μL, and nine modular units successfully detected the target pathogens. The MRT-NAAT AMR set included 24 modular units 65-785bp in product size with a Tms of 75.5-87.5°C; it showed high performance for detecting GPP target genes and variants. MRT-NAAT enables pathogen identification and AMR gene detection and is time-effective. By unifying the reaction settings of each modular unit, the modularity where combinations of primers can be used according to need could be achieved. This would greatly help in reflecting the researcher's need and the AMR status of a certain region while successfully detecting pathogens and AMR genes.

Historical milestone in 42 years of viral sequencing-Impetus for a community-driven sequencing of global priority pathogens.

OPINION article Front. Microbiol., 04 November 2022Sec. Infectious Agents and Disease Volume 13 - 2022 | https://doi.org/10.3389/fmicb.2022.1020148

Colonization dynamics of extended-spectrum beta-lactamase-producing Enterobacterales in the gut of Malawian adults

Drug-resistant bacteria of the order Enterobacterales which produce extended-spectrum beta-lactamase enzymes (ESBL-Enterobacterales, ESBL-E) are global priority pathogens. Antimicrobial stewardship interventions proposed to curb their spread include shorter courses of antimicrobials to reduce selection pressure but individual-level acquisition and selection dynamics are poorly understood. We sampled stool of 425 adults (aged 16–76 years) in Blantyre, Malawi, over 6 months and used multistate modelling and whole-genome sequencing to understand colonization dynamics of ESBL-E. Models suggest a prolonged effect of antimicrobials such that truncating an antimicrobial course at 2 days has a limited effect in reducing colonization. Genomic analysis shows largely indistinguishable diversity of healthcare-associated and community-acquired isolates, hence some apparent acquisition of ESBL-E during hospitalization may instead represent selection from a patient’s microbiota by antimicrobial exposure. Our approach could help guide stewardship protocols; interventions that aim to review and truncate courses of unneeded antimicrobials may be of limited use in preventing ESBL-E colonization.

Heteroaryl-Ethylenes as New Effective Agents for High Priority Gram-Positive and Gram-Negative Bacterial Clinical Isolates

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumannii. Furthermore, an ATCC control strain was selected for all species tested. The MIC tests were performed according to the standard method. The PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0.12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4–64 mg/L) but still promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. Our study contributes to the search for new molecules that can fight bacterial infections, in particular those caused by MDR bacteria in hospitals. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.

Bacterial Antibiotic Resistance: The Most Critical Pathogens.

Antibiotics have made it possible to treat bacterial infections such as meningitis and bacteraemia that, prior to their introduction, were untreatable and consequently fatal. Unfortunately, in recent decades overuse and misuse of antibiotics as well as social and economic factors have accelerated the spread of antibiotic-resistant bacteria, making drug treatment ineffective. Currently, at least 700,000 people worldwide die each year due to antimicrobial resistance (AMR). Without new and better treatments, the World Health Organization (WHO) predicts that this number could rise to 10 million by 2050, highlighting a health concern not of secondary importance. In February 2017, in light of increasing antibiotic resistance, the WHO published a list of pathogens that includes the pathogens designated by the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) to which were given the highest “priority status” since they represent the great threat to humans. Understanding the resistance mechanisms of these bacteria is a key step in the development of new antimicrobial drugs to tackle drug-resistant bacteria. In this review, both the mode of action and the mechanisms of resistance of commonly used antimicrobials will be examined. It also discusses the current state of AMR in the most critical resistant bacteria as determined by the WHO’s global priority pathogens list.

Whole genome sequence analysis of Shigella from Malawi identifies fluoroquinolone resistance.

Increasing antimicrobial resistance and limited alternative treatments have led to fluoroquinolone-resistant Shigella strain inclusion on the WHO global priority pathogens list. In this study we characterized multiple Shigella isolates from Malawi with whole genome sequence analysis, identifying the acquirable fluoroquinolone resistance determinant qnrS1.

Carbapenemases as factors of Resistance to Antibacterial Drugs

Antibiotic drugs are used to treat and prevent bacterial infections around the world. The emergence and spread of bacterial resistance to carbapenems is currently a real threat that determines the need for its timely detection and suppression. Carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as the highest priority in the 2017 WHO Global Priority Pathogens List. The number of known carbapenemases is constantly increasing, but the most common are IMP-type, VIM-type, NDM-type, KPC-type, and OXA-type. Carbapenemases belong to molecular class B (metallo-β-lactamases) or molecular classes A and D (serine carbapenemases). The genes encoding carbapenemases are part of the mobile genetic elements, which contributes to their rapid intra- and interspecific transfer. In this regard, the purpose of this review is to get acquainted with the current information on the classification and characteristics of carbapenemases, ways to overcome the spread of resistance to carbapenems. At the same time, the article pays attention not only to infectious agents, but also to those carriers of carbapenemases that have not been seen as infectious agents, since they can also influence the evolution of resistance genes.

Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds.

SummaryAs a promising target for alternative antimicrobials, bacterial recombinase A (RecA) protein has attracted much attention for its roles in antibiotic-driven SOS response and mutagenesis. Naphthalene polysulfonated compounds (NPS) such as suramin have previously been explored as antibiotic adjuvants targeting RecA, although the underlying structural bases for RecA-ligand interactions remain obscure. Based on our in silico predictions and documented activity of NPS in vitro, we conclude that the analyzed NPS likely interact with Tyr103 (Y103) and other key residues in the ATPase activity center (pocket A). For validation, we generated recombinant RecA proteins (wild-type versus Y103 mutant) to determine the binding affinities for RecA protein interactions with suramin and underexamined NPS in isothermal titration calorimetry. The corresponding dissociation constants (Kd) ranged from 11.5 to 18.8 μM, and Y103 was experimentally shown to be critical to RecA-NPS interactions.

Global priority multidrug-resistant pathogens do not resist photodynamic therapy

Microbial drug-resistance demands immediate implementation of novel therapeutic strategies. Antimicrobial photodynamic therapy (aPDT) combines the administration of a photosensitizer (PS) compound with low-irradiance light to induce photochemical reactions that yield reactive oxygen species (ROS). Since ROS react with nearly all biomolecules, aPDT offers a powerful multitarget method to avoid selection of drug-resistant strains. In this study, we assayed photodynamic inactivation under a standardized method, combining methylene blue (MB) as PS and red light, against global priority pathogens. The species tested include Acinetobacter baumannii, Klebsiella aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans. Our strain collection presents resistance to all tested antimicrobials (>50). All drug-resistant strains were compared to their drug-sensitive counterparts. Regardless of resistance phenotype, MB-aPDT presented species-specific dose-response kinetics. More than 5log10 reduction was observed within less than 75 s of illumination for A. baumannii, E. coli, E. faecium, E. faecalis and S. aureus and within less than 7 min for K. aerogenes, K. pneumoniae, P. aeruginosa, C. albicans and C. neoformans. No signs of correlations in between drug-resistance profiles and aPDT sensitivity were observed. Therefore, MB-aPDT can provide effective therapeutic protocols for a very broad spectrum of pathogens. Hence, we believe that this study represents a very important step to bring aPDT closer to implementation into mainstream medical practices.

Global priority pathogens: virulence, antimicrobial resistance and prospective treatment options.

Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Salmonella spp. are part of a group of pathogens that pose a major threat to human health due to the emergence of multidrug-resistant strains. Moreover, these bacteria have several virulence factors that allow them to successfully colonize their hosts, such as toxins and the ability to produce biofilms, resulting in an urgent need to develop new strategies to fight these pathogens. In this review, we compile the most up-to-date information on the epidemiology, virulence and resistance of these clinically important microorganisms. Additionally, we address new therapeutic alternatives, with a focus on molecules with antivirulence activity, which are considered promising to combat multidrug-resistant bacteria.