# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 2505 | 0 | 0.9235 | Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting. | 2006 | 16813979 |
| 2504 | 1 | 0.9235 | Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting. | 2006 | 16735148 |
| 2105 | 2 | 0.9208 | Infections Caused by Antimicrobial Drug-Resistant Saprophytic Gram-Negative Bacteria in the Environment. BACKGROUND: Drug-resistance genes found in human bacterial pathogens are increasingly recognized in saprophytic Gram-negative bacteria (GNB) from environmental sources. The clinical implication of such environmental GNBs is unknown. OBJECTIVES: We conducted a systematic review to determine how often such saprophytic GNBs cause human infections. METHODS: We queried PubMed for articles published in English, Spanish, and French between January 2006 and July 2014 for 20 common environmental saprophytic GNB species, using search terms "infections," "human infections," "hospital infection." We analyzed 251 of 1,275 non-duplicate publications that satisfied our selection criteria. Saprophytes implicated in blood stream infection (BSI), urinary tract infection (UTI), skin and soft tissue infection (SSTI), post-surgical infection (PSI), osteomyelitis (Osteo), and pneumonia (PNA) were quantitatively assessed. RESULTS: Thirteen of the 20 queried GNB saprophytic species were implicated in 674 distinct infection episodes from 45 countries. The most common species included Enterobacter aerogenes, Pantoea agglomerans, and Pseudomonas putida. Of these infections, 443 (66%) had BSI, 48 (7%) had SSTI, 36 (5%) had UTI, 28 (4%) had PSI, 21 (3%) had PNA, 16 (3%) had Osteo, and 82 (12%) had other infections. Nearly all infections occurred in subjects with comorbidities. Resistant strains harbored extended-spectrum beta-lactamase (ESBL), carbapenemase, and metallo-β-lactamase genes recognized in human pathogens. CONCLUSION: These observations show that saprophytic GNB organisms that harbor recognized drug-resistance genes cause a wide spectrum of infections, especially as opportunistic pathogens. Such GNB saprophytes may become increasingly more common in healthcare settings, as has already been observed with other environmental GNBs such as Acinetobacter baumannii and Pseudomonas aeruginosa. | 2017 | 29164118 |
| 3761 | 3 | 0.9206 | Stenotrophomonas maltophilia as an Emerging Ubiquitous Pathogen: Looking Beyond Contemporary Antibiotic Therapy. Stenotrophomonas maltophilia is a commensal and an emerging pathogen earlier noted in broad-spectrum life threatening infections among the vulnerable, but more recently as a pathogen in immunocompetent individuals. The bacteria are consistently being implicated in necrotizing otitis, cutaneous infections including soft tissue infection and keratitis, endocarditis, meningitis, acute respiratory tract infection (RTI), bacteraemia (with/without hematological malignancies), tropical pyomyositis, cystic fibrosis, septic arthritis, among others. S. maltophilia is also an environmental bacteria occurring in water, rhizospheres, as part of the animals' microflora, in foods, and several other microbiota. This review highlights clinical reports on S. maltophilia both as an opportunistic and as true pathogen. Also, biofilm formation as well as quorum sensing, extracellular enzymes, flagella, pili/fimbriae, small colony variant, other virulence or virulence-associated factors, the antibiotic resistance factors, and their implications are considered. Low outer membrane permeability, natural MDR efflux systems, and/or resistance genes, resistance mechanisms like the production of two inducible chromosomally encoded β-lactamases, and lack of carefully compiled patient history are factors that pose great challenges to the S. maltophilia control arsenals. The fluoroquinolone, some tetracycline derivatives and trimethoprim-sulphamethaxole (TMP-SMX) were reported as effective antibiotics with good therapeutic outcome. However, TMP-SMX resistance and allergies to sulfa together with high toxicity of fluoroquinolone are notable setbacks. S. maltophilia's production and sustenance of biofilm by quorum sensing enhance their virulence, resistance to antibiotics and gene transfer, making quorum quenching an imperative step in Stenotrophomonas control. Incorporating several other proven approaches like bioengineered bacteriophage therapy, Epigallocatechin-3-gallate (EGCG), essential oil, nanoemulsions, and use of cationic compounds are promising alternatives which can be incorporated in Stenotrophomonas control arsenal. | 2017 | 29250041 |
| 4819 | 4 | 0.9199 | Gram-Negative Bacteria. Gram-negative bacteria (GNB) are among the world's most significant public health problems due to their high resistance to antibiotics. These microorganisms have significant clinical importance in hospitals because they put patients in the intensive care unit (ICU) at high risk and lead to high morbidity and mortality. Two large groups, Enterobacteriaceae and the non-fermenters, are responsible for most clinical isolates; nevertheless, other clinically concerning gram-negative organisms exist, including but not limited to Neisseria, Haemophilus spp., Helicobacter pylori, and Chlamydia trachomatis. Enterobacteriaceae Enterobacteriaceae are a heterogeneous group widely dispersed in nature. They account for about 80% of gram-negative isolates with a myriad of disease-causing general/species in humans, including urinary tract infections, pneumonia, diarrhea, meningitis, sepsis, endotoxic shock, and many others. The general/species that frequently affect humans are Escherichia, Proteus, Enterobacter, Klebsiella, Citrobacter, Yersinia, Shigella, and Salmonella, among others. Laboratory characterization is an essential component when it comes to microorganisms; therefore, it is imperative to expose characteristics of Enterobacteriaceae, which are bacilli, non-sporulated, have variable motility, grow in the presence and absence of oxygen, ferment organisms of glucose, are cytochrome oxidase negative, and can reduce nitrate to nitrite. Non-Fermenters The non-fermenter, gram-negative bacilli (BNF) have a lower frequency of isolation when compared to Enterobacteriaceae; however, they are a relevant group since they cause severe, fatal infections, especially in the hospital environment. They also cause opportunistic diseases in ICU patients who undergo invasive procedures. The main BNF microorganisms that cause human disease are Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cepacia, Burkholderia pseudomallei, Stenotrophomonas., Alcaligenes, and Moraxella. These stand out for being aerobic and non-sporulated; they are incapable of fermenting sugars, using them through the oxidative route. The critical issue regarding BNF, when it comes to the antimicrobial sensitivity profile, is undoubtedly their intrinsic resistance since they produce a variety of genes with multiple mechanisms capable of mitigating the microbicidal action. Thus, it stands out in P. aeruginosa, cephalosporinase of type AmpC, and efflux systems that confer resistance to b-lactams. The most frequent are MexAB-OprM; and loss of OprD (which gives impermeability to the bacterial cell due to the loss of porin.) Acinetobacter baumannii naturally produces AmpC cephalosporinase and oxacillinase (OXA), leaving it spontaneously immune to many drugs. The genetic ingenuity of this microorganism goes further, and it combines high impermeability with genetic plasticity, combining with the resistance of mechanisms such as extended-spectrum b-lactamases (ESBL). The Stenotrophomonas exhibit a pattern of intrinsic multi-resistance, especially in patients who have had contact with carbapenems. Thus, Stenotrophomonas present several efflux pumps and produce two carbapenemases – L1 (resistance to all carbapenems) and L2 (cephalosporinase). These mechanisms, associated or separate, restrict the treatment options to an alarming level. Sulfamethoxazole-trimethoprim remains the mainstay of treatment. Antibiotic Resistance These organisms have a range of mechanisms to prevent the action of many antimicrobials used in clinical medicine. Some of the mechanisms of resistance include efflux pumps, alteration of the drug binding site and membrane permeability, degradation enzymes, and the conformational change of the drug culminating in its inactivation. GNB have two membranes, an external and an internal. The external membrane expresses a potent immune response inducer, lipopolysaccharide (LPS), which is composed of three units: a hydrophilic polysaccharide, O antigen, and a hydrophobic domain known as lipid A. Lipid A are responsible for the higher endotoxic activity of these bacteria. However, the LPS is heterogeneous in the various bacterial groups, and some bacteria manifest this antigen weakly due to genetic changes and are not recognized by Toll-like receptors. In contrast, there are BGN groups that can trigger such a response in large proportions. Thus, LPS can trigger the innate immune response through Toll-like receptors 4 (TLR4), which occurs in many immune cells such as monocytes, macrophages, dendritic cells, and neutrophils. The resulting activation of the innate immune response mediated by LPS together with TLR4 receptors culminates in an exacerbated response with the production of cytokines, chemokines, and interferons and their suppression. Enterobacteriaceae diffuse their plasmids by conjugation, which gives rise to resistance to almost all existing antibiotics. The family of enzymes carbapenemase – KPC, NDM-1, IMP, VIM, OXA-48 – is undoubtedly one of the most significant health challenges of the century, given the potential for dissemination between species and mortality rates due to infections caused by bacteria with such plasmids. Colistin, one of the few antibiotics that still treat multiresistant infections, already has a mobile resistance gene, mcr-1, and Enterobacteriaceae has a crucial role in the spread of this gene, with worldwide reports. Moreover, a further concern is that they usually associate these genes with other resistance genes (CTX-M, NDM, IMP), producing resistance to cephalosporins and carbapenems, enhancing the deleterious effects caused by these microorganisms. | 2025 | 30855801 |
| 8438 | 5 | 0.9197 | Virulence of Bacteria Colonizing Vascular Bundles in Ischemic Lower Limbs. BACKGROUND: We documented previously the presence of bacterial flora in vascular bundles, lymphatics, and lymph nodes of ischemic lower limbs amputated because of multifocal atheromatic changes that made them unsuitable for reconstructive surgery and discussed their potential role in tissue destruction. The question arose why bacterial strains inhabiting lower limb skin and considered to be saprophytes become pathogenic once they colonize deep tissues. Bacterial pathogenicity is evoked by activation of multiple virulence factors encoded by groups of genes. METHODS: We identified virulence genes in bacteria cultured from deep tissue of ischemic legs of 50 patients using a polymerase chain reaction technique. RESULTS: The staphylococcal virulence genes fnbA (fibronectin-binding protein A), cna (collagen adhesin precursor), and ica (intercellular adhesion) were present in bacteria isolated from both arteries and, to a lesser extent, skin. The IS256 gene, whose product is responsible for biofilm formation, was more frequent in bacteria retrieved from the arteries than skin bacteria. Among the virulence genes of Staphylococcus epidermidis encoding autolysin atlE, icaAB (intercellular adhesion), and biofilm insert IS256, only the latter was detected in arterial specimens. Bacteria cultured from the lymphatics did not reveal expression of eta and IS256 in arteries. The Enterococcus faecalis asa 373 (aggregation substance) and cylA (cytolysin activator) frequency was greater in arteries than in skin bacteria, as were the E. faecium cyl A genes. All Pseudomonas aeruginosa virulence genes were present in bacteria cultured from both the skin and arteries. Staphylococci colonizing arterial bundles and transported to tissues via ischemic limb lymphatics expressed virulence genes at greater frequency than did those dwelling on the skin surface. Moreover, enterococci and Pseudomonas isolated from arterial bundles expressed many virulence genes. CONCLUSIONS: These findings may add to the understanding of the mechanism of development of destructive changes in lower limb ischemic tissues by the patient's, but not hospital-acquired, bacteria, as well as the generally unsatisfactory results of antibiotic administration in these cases. More aggressive antibiotic therapy targeted at the virulent species should be applied. | 2016 | 26431369 |
| 6045 | 6 | 0.9194 | Lacticaseicin 30 and Colistin as a Promising Antibiotic Formulation against Gram-Negative β-Lactamase-Producing Strains and Colistin-Resistant Strains. Antimicrobial resistance is a global health concern across the world and it is foreseen to swell if no actions are taken now. To help curbing this well announced crisis different strategies are announced, and these include the use of antimicrobial peptides (AMP), which are remarkable molecules known for their killing activities towards pathogenic bacteria. Bacteriocins are ribosomally synthesized AMP produced by almost all prokaryotic lineages. Bacteriocins, unlike antibiotics, offer a set of advantages in terms of cytotoxicity towards eukaryotic cells, their mode of action, cross-resistance and impact of microbiota content. Most known bacteriocins are produced by Gram-positive bacteria, and specifically by lactic acid bacteria (LAB). LAB-bacteriocins were steadily reported and characterized for their activity against genetically related Gram-positive bacteria, and seldom against Gram-negative bacteria. The aim of this study is to show that lacticaseicin 30, which is one of the bacteriocins produced by Lacticaseibacillus paracasei CNCM I-5369, is active against Gram-negative clinical strains (Salmonella enterica Enteritidis H10, S. enterica Typhimurium H97, Enterobacter cloacae H51, Escherichia coli H45, E. coli H51, E. coli H66, Klebsiella oxytoca H40, K. pneumoniae H71, K. variicola H77, K. pneumoniae H79, K. pneumoniae H79), whereas antibiotics failed. In addition, lacticaseicin 30 and colistin enabled synergistic interactions towards the aforementioned target Gram-negative clinical strains. Further, the combinations of lacticaseicin 30 and colistin prompted a drastic downregulation of mcr-1 and mcr-9 genes, which are associated with the colistin resistance phenotypes of these clinical strains. This report shows that lacticaseicin 30 is active against Gram-negative clinical strains carrying a rainbow of mcr genes, and the combination of these antimicrobials constitutes a promising therapeutic option that needs to be further exploited. | 2021 | 35052897 |
| 2096 | 7 | 0.9192 | Investigation of isepamicin in vitro efficiency in Gram negative bacteria efficacy of isepamicin. CONTEXT: Isepamicin is a new semisynthetic aminoglycoside derived from gentamicin B and it is effective against Gram negative bacteria. Antibiotic resistance is an emerging problem and new options need for the treatment of infections caused by Gram negative bacteria. AIMS: In this study we aimed to investigate the in vitro efficiency in carbapenem susceptible and nonsusceptible Enterobacterales and Pseudomonas aeruginosa. METHODS AND MATERIAL: A total of 214 isolates of Gram-negative bacteria (Enterobacterales n = 129 and P. aeruginosa n = 85). Identification of the bacteria was tested in Vitek MS (Biomeriux, France). Susceptibility of isepamicin, amikacin, gentamicin, tobramycin and netilmicin was determined by Kirby Bauer disc diffusion method. The breakpoints for susceptibility to isepamicin, amikacin, gentamicin, streptomycin, tobramycin and netilmicin were evaluated according to the Comité de l'Antibiogramme dela Société Française de Microbiologie (CA-SFM) and EUCAST, respectively. Aminoglycoside modifying enzyme (AME) genes were investigated by multiplex PCR method. RESULTS: Isepamicin susceptibility was determined as 92.3% for Enterobacterales and 67% for P. aeruginosa and 94.4% for carbapenem resistant Enterobacterales. The most common AME gene was aac (6')-Ib in both Enterobacterales (76%) and P. aeruginosa (14.1%). Seven of the isepamicin intermediate or resistant isolates were positive aac (6')-Ib in Enterobacterales and P. aeruginosa. CONCLUSIONS: In this study, isepamicin showed good efficiency against both susceptible and carbapenem nonsusceptible Enterobacterales. But amikacin was prior to isepamicin P. aeruginosa isolates. Isepamicin could be a therapeutic option for the infections caused by Enterobacterales. | 2021 | 33610258 |
| 9022 | 8 | 0.9191 | Drug repositioning: doxazosin attenuates the virulence factors and biofilm formation in Gram-negative bacteria. The resistance development is an increasing global health risk that needs innovative solutions. Repurposing drugs to serve as anti-virulence agents is suggested as an advantageous strategy to diminish bacterial resistance development. Bacterial virulence is controlled by quorum sensing (QS) system that orchestrates the expression of biofilm formation, motility, and virulence factors production as enzymes and virulent pigments. Interfering with QS could lead to bacterial virulence mitigation without affecting bacterial growth that does not result in bacterial resistance development. This study investigated the probable anti-virulence and anti-QS activities of α-adrenoreceptor blocker doxazosin against Proteus mirabilis and Pseudomonas aeruginosa. Besides in silico study, in vitro and in vivo investigations were conducted to assess the doxazosin anti-virulence actions. Doxazosin significantly diminished the biofilm formation and release of QS-controlled Chromobacterium violaceum pigment and virulence factors in P. aeruginosa and P. mirabilis, and downregulated the QS encoding genes in P. aeruginosa. Virtually, doxazosin interfered with QS proteins, and in vivo protected mice against P. mirabilis and P. aeruginosa. The role of the membranal sensors as QseC and PmrA was recognized in enhancing the Gram-negative virulence. Doxazosin downregulated the membranal sensors PmR and QseC encoding genes and could in silico interfere with them. In conclusion, this study preliminary documents the probable anti-QS and anti-virulence activities of doxazosin, which indicate its possible application as an alternative or in addition to antibiotics. However, extended toxicological and pharmacological investigations are essential to approve the feasible clinical application of doxazosin as novel efficient anti-virulence agent. KEY POINTS: • Anti-hypertensive doxazosin acquires anti-quorum sensing activities • Doxazosin diminishes the virulence of Proteus mirabilis and Pseudomonas aeruginosa • Doxazosin could dimmish the bacterial espionage. | 2023 | 37079062 |
| 8160 | 9 | 0.9190 | Quorum Sensing in Gram-Negative Bacteria: Strategies to Overcome Antibiotic Resistance in Ocular Infections. Truly miraculous medications and antibiotics have helped save untold millions of lives. Antibiotic resistance, however, is a significant issue related to health that jeopardizes the effectiveness of antibiotics and could harm everyone's health. Bacteria, not humans or animals, become antibiotic-resistant. Bacteria use quorum-sensing communication routes to manage an assortment of physiological exercises. Quorum sensing is significant for appropriate biofilm development. Antibiotic resistance occurs when bacteria establish a biofilm on a surface, shielding them from the effects of infection-fighting drugs. Acylated homoserine lactones are used as autoinducers by gram-negative microscopic organisms to impart. However, antibiotic resistance among ocular pathogens is increasing worldwide. Bacteria are a significant contributor to ocular infections around the world. Gram-negative microscopic organisms are dangerous to ophthalmic tissues. This review highlights the use of elective drug targets and treatments, for example, combinational treatment, to vanquish antibiotic-resistant bacteria. Also, it briefly portrays anti-biotic resistance brought about by gram-negative bacteria and approaches to overcome resistance with the help of quorum sensing inhibitors and nanotechnology as a promising medication conveyance approach to give insurance of anti-microbials and improve pathways for the administration of inhibitors of quorum sensing with a blend of anti-microbials to explicit target destinations and penetration through biofilms for treatment of ocular infections. It centres on the methodologies to sidestep the confinements of ocular anti-biotic delivery with new visual innovation. | 2024 | 37497706 |
| 3762 | 10 | 0.9190 | The epidemiology of antimicrobial resistance and transmission of cutaneous bacterial pathogens in domestic animals. As the primary agents of skin and soft tissue infections in animals, Staphylococcus spp and Pseudomonas aeruginosa are among the most formidable bacterial pathogens encountered by veterinarians. Staphylococci are commensal inhabitants of the surfaces of healthy skin and mucous membranes, which may gain access to deeper cutaneous tissues by circumventing the stratum corneum's barrier function. Compromised barrier function occurs in highly prevalent conditions such as atopic dermatitis, endocrinopathies, and skin trauma. P aeruginosa is an environmental saprophyte that constitutively expresses virulence and antimicrobial resistance genes that promote its success as an animal pathogen. For both organisms, infections of the urinary tract, respiratory tract, joints, central nervous system, and body cavities may occur through ascension along epithelial tracts, penetrating injuries, or hematogenous spread. When treating infections caused by these pathogens, veterinarians now face greater therapeutic challenges and more guarded outcomes for our animal patients because of high rates of predisposing factors for infection and the broad dissemination of antimicrobial resistance genes within these bacterial species. This review considers the history of the rise and expansion of multidrug resistance in staphylococci and P aeruginosa and the current state of knowledge regarding the epidemiologic factors that underly the dissemination of these pathogens across companion animal populations. Given the potential for cross-species and zoonotic transmission of pathogenic strains of these bacteria, and the clear role played by environmental reservoirs and fomites, a one-health perspective is emphasized. | 2023 | 36917615 |
| 9989 | 11 | 0.9189 | Molecular Insights into Fungal Innate Immunity Using the Neurospora crassa - Pseudomonas syringae Model. Recent comparative genomics and mechanistic analyses support the existence of a fungal immune system. Fungi encode genes with features similar to non-self recognition systems in plants, animals, and bacteria. However, limited functional or mechanistic evidence exists for the surveillance-system recognition of heterologous microbes in fungi. We found that Neurospora species coexist with Pseudomonas in their natural environment. We leveraged two model organisms, Neurospora crassa and Pseudomonas syringae DC3000 (PSTDC3000) to observe immediate fungal responses to bacteria. PSTDC3000 preferentially surrounds N. crassa cells on a solid surface, causing environmental dependent growth responses, bacterial proliferation and varying fungal fitness. Specifically, the Type III secretion system (T3SS) ΔhrcC mutant of PSTDC3000 colonized N. crassa hyphae less well. To dissect initial cellular signaling events within the population of germinated asexual spores (germlings), we performed transcriptomics on N. crassa after PSTDC3000 inoculation. Upon contact with live bacteria, a subpopulation of fungal germlings initiate a response as early as ten minutes post-contact revealing transcriptional differentiation of Reactive Oxygen Species (ROS) mechanisms, trace metal warfare, cell wall remodeling dynamics, multidrug-efflux transporters, secondary metabolite synthesis, and excretion. We dissected mutants of plausible receptors, signaling pathways, and responses that N. crassa uses to detect and mount a defense against PSTDC3000 and found seven genes that influence resistant and susceptibility phenotypes of N. crassa to bacterial colonization. Mutants in genes encoding a ctr copper transporter ( tcu-1 ), ferric reductase ( fer-1 ), superoxide reductase ( sod-2 ), multidrug resistance transporter ( mdr-6 ), a secreted lysozyme-Glycoside hydrolase ( lyz ) and the Woronin body tether leashin (NCU02793, lah-1 and lah-2 ) showed a significant reduction of growth in the presence of bacteria, allowing the bacteria to fully take over the fungal mycelium faster than wildtype. In this study we provide a bacterial-fungal model system within Dikarya that allows us to begin to dissect signaling pathways of the putative fungal immune system. | 2025 | 39896647 |
| 6650 | 12 | 0.9189 | Antibiotic resistance is never going to go away. No matter how many drugs we throw at it, no matter how much money and resources are sacrificed to wage a war on resistance, it will always prevail. Humans are forced to coexist with the fact of antibiotic resistance. Public health officials, clinicians, and scientists must find effective ways to cope with antibiotic resistant bacteria harmful to humans and animals and to control the development of new types of resistance. The American Academy of Microbiology convened a colloquium October 12–14, 2008, to discuss antibiotic resistance and the factors that influence the development and spread of resistance. Participants, whose areas of expertise included medicine, microbiology, and public health, made specific recommendations for needed research, policy development, a surveillance network, and treatment guidelines. Antibiotic resistance issues specific to the developing world were discussed and recommendations for improvements were made. Each antibiotic is injurious only to a certain segment of the microbial world, so for a given antibacterial there are some species of bacteria that are susceptible and others not. Bacterial species insusceptible to a particular drug are “naturally resistant.” Species that were once sensitive but eventually became resistant to it are said to have “acquired resistance.” It is important to note that “acquired resistance” affects a subset of strains in the entire species; that is why the prevalence of “acquired resistance” in a species is different according to location. Antibiotic resistance, the acquired ability of a pathogen to withstand an antibiotic that kills off its sensitive counterparts, originally arises from random mutations in existing genes or from intact genes that already serve a similar purpose. Exposure to antibiotics and other antimicrobial products, whether in the human body, in animals, or the environment, applies selective pressure that encourages resistance to emerge favoring both “naturally resistant” strains and strains which have “acquired resistance.” Horizontal gene transfer, in which genetic information is passed between microbes, allows resistance determinants to spread within harmless environmental or commensal microorganisms and pathogens, thus creating a reservoir of resistance. Resistance is also spread by the replication of microbes that carry resistance genes, a process that produces genetically identical (or clonal) progeny. Rapid diagnostic methods and surveillance are some of the most valuable tools in preventing the spread of resistance. Access to more rapid diagnostic tests that could determine the causative agent and antibiotic susceptibility of infections would inform better decision making with respect to antibiotic use, help slow the selection of resistant strains in clinical settings, and enable better disease surveillance. A rigorous surveillance network to track the evolution and spread of resistance is also needed and would probably result in significant savings in healthcare. Developing countries face unique challenges when it comes to antibiotic resistance; chief among them may be the wide availability of antibiotics without a prescription and also counterfeit products of dubious quality. Lack of adequate hygiene, poor water quality, and failure to manage human waste also top the list. Recommendations for addressing the problems of widespread resistance in the developing world include: proposals for training and infrastructure capacity building; surveillance programs; greater access to susceptibility testing; government controls on import, manufacture and use; development and use of vaccines; and incentives for pharmaceutical companies to supply drugs to these countries. Controlling antibiotic resistant bacteria and subsequent infections more efficiently necessitates the prudent and responsible use of antibiotics. It is mandatory to prevent the needless use of antibiotics (e.g., viral infections; unnecessary prolonged treatment) and to improve the rapid prescription of appropriate antibiotics to a patient. Delayed or inadequate prescriptions reduce the efficacy of treatment and favor the spread of the infection. Prudent use also applies to veterinary medicine. For example, antibiotics used as “growth promoters” have been banned in Europe and are subject to review in some other countries. There are proven techniques for limiting the spread of resistance, including hand hygiene, but more rapid screening techniques are needed in order to effectively track and prevent spread in clinical settings. The spread of antibiotic resistance on farms and in veterinary hospitals may also be significant and should not be neglected. Research is needed to pursue alternative approaches, including vaccines, antisense therapy, public health initiatives, and others. The important messages about antibiotic resistance are not getting across from scientists and infectious diseases specialists to prescribers, stakeholders, including the public, healthcare providers, and public officials. Innovative and effective communication initiatives are needed, as are carefully tailored messages for each of the stakeholder groups. | 2009 | 32644325 |
| 223 | 13 | 0.9189 | Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria. Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy. | 2023 | 37760679 |
| 9789 | 14 | 0.9188 | Nosocomial antibiotic resistance in multiple gram-negative species: experience at one hospital with squeezing the resistance balloon at multiple sites. Increased use of antibiotics has led to the isolation of multidrug-resistant bacteria, especially in intensive care units and long-term care facilities. Resistance in specific gram-negative bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, is of great concern, because a growing number of reports have documented mechanisms whereby these microorganisms have become resistant to all available antibacterial agents used in therapy. Reduction in the selection of these multidrug-resistant bacteria can be accomplished by a combination of several strategies. These include having an understanding of the genetics of both innate and acquired characteristics of bacteria; knowing resistance potentials for specific antibacterials; monitoring resistance trends in bacteria designated as problematic organisms within a particular institution on a routine basis; modifying antibiotic formularies when and where needed; creating institutional education programs; and enforcing strict infection-control practices. Strategies appropriate for primary prevention of nosocomial resistance may differ from those required for control of existing epidemic or endemic resistance. | 2002 | 11797177 |
| 2496 | 15 | 0.9188 | Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance. The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii. | 2020 | 32971809 |
| 9810 | 16 | 0.9187 | Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies. Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill. | 2023 | 39816646 |
| 9760 | 17 | 0.9186 | Mutations leading to ceftolozane/tazobactam and imipenem/cilastatin/relebactam resistance during in vivo exposure to ceftazidime/avibactam in Pseudomonas aeruginosa. Identifying resistance mechanisms to novel antimicrobials informs treatment strategies during infection and antimicrobial development. Studying resistance that develops during the treatment of an infection can provide the most clinically relevant mutations conferring resistance, but cross-sectional studies frequently identify multiple candidate resistance mutations without resolving the driver mutation. We performed whole-genome sequencing of longitudinal Pseudomonas aeruginosa from a patient whose P. aeruginosa developed imipenem/cilastatin/relebactam and ceftolozane/tazobactam resistance during ceftazidime/avibactam treatment. This analysis determined new mutations that arose in isolates resistant to both imipenem/cilastatin/relebactam and ceftolozane/tazobactam. Mutations in penicillin-binding protein 3 ftsI, the MexAB-OprM repressor nalD, and a virulence regulator pvdS were found in resistant isolates. Importantly, drug efflux was not increased in the resistant isolate compared to the most closely related susceptible isolates. We conclude that mutations in peptidoglycan synthesis genes can alter the efficacy of multiple antimicrobials. IMPORTANCE: Antibiotic resistance is a significant challenge for physicians trying to treat infections. The development of novel antibiotics to treat resistant infections has not been prioritized for decades, limiting treatment options for infections caused by many high-priority pathogens. Cross-resistance, when one mutation provides resistance to multiple antibiotics, is most problematic. Mutations that cause cross-resistance need to be considered when developing new antibiotics to guide developers toward drugs with different targets, and thus a better likelihood of efficacy. This work was undertaken to determine the mutation that caused resistance to three antibiotics for highly resistant Pseudomonas aeruginosa infection treatment while the bacteria were exposed to only one of these agents. The findings provide evidence that drug developers should endeavor to find effective antibiotics with new targets and that medical providers should utilize medications with different mechanisms of action in bacteria that have become resistant to even one of these three agents. | 2025 | 39932323 |
| 9790 | 18 | 0.9186 | Emerging antibiotic resistance: carbapenemase-producing enterobacteria. Bad new bugs, still no new drugs. Antimicrobial resistance (AMR) is a global health security threat requiring actions across government sectors and society. Many factors are involved in this phenomenon, being overuse of antibiotics, incorrect antibiotic prophylaxis, and use of antibiotics for zootechnic reasons the main causes of the increasing rate of multi-drug resistant (MDR) bacteria. The impact of resistance to antimicrobials is an important threat due also to the emergence of MDR Gram-negative bacteria resistant to carbapenems, and the lack of the research for new active molecules. The production of extended spectrum beta-lactamase enzymes has been the first threatening mechanism for Gram-negative resistance to antibiotics, which prompted the development of new classes of antibiotics such as carbapenems. Unfortunately, resistance to carbapenems developed because of multiple mechanisms including efflux pumps, porin mutations and enzyme production, being the latter particularly relevant in terms of diffusion due to the genes located within plasmids that drive their horizontal diffusion. In this scenario, antimicrobial stewardship programs (ASP) are a mandatory resource in fighting the resistance spread. The reduction of total amount of antibiotics administration in the hospital setting and guiding prescribers in the correct administration of antibiotics for the smallest period possible, at the correct dosage, can be defined as the first goals of an ASP. Anyway, in an efficacious ASP, apart from antibiotic administration, efforts must been made in ensuring the lowest probability of spreading of MDR by efficacious measures of isolation of carriers, and by offering tools for a rapid diagnosis of viral infections avoiding the administration of unnecessary antibiotics. A continuous audit of the ASP programs and a correct assessment of the allergy to drugs such as penicillin have to complete the program. Currently, only a few options are available for patients with an infection sustained by Gram-negative MDR bacteria. All the options actually available are based on the administration of colystin, an old drug whose real efficacy is reduced due to its relevant toxicity, or on the administration of recently proposed drugs such as ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. All these new drugs do not have a novel mechanism of action and have limited spectrum in term of activity against MDR bacteria. In conclusion, antimicrobial resistance is a global emergence and AMP is the most powerful tool actually available. Few limited options are available to treat infections due to Carbapenem Resistant Enterobacteria. Antimicrobial molecules with true novel mechanism of action are needed to win the fight against antimicrobial resistance. | 2019 | 31846984 |
| 1546 | 19 | 0.9185 | Bench-to-bedside review: The role of beta-lactamases in antibiotic-resistant Gram-negative infections. Multidrug resistance has been increasing among Gram-negative bacteria and is strongly associated with the production of both chromosomal- and plasmid-encoded beta-lactamases, whose number now exceeds 890. Many of the newer enzymes exhibit broad-spectrum hydrolytic activity against most classes of beta-lactams. The most important plasmid-encoded beta-lactamases include (a) AmpC cephalosporinases produced in high quantities, (b) the expanding families of extended-spectrum beta-lactamases such as the CTX-M enzymes that can hydrolyze the advanced-spectrum cephalosporins and monobactams, and (c) carbapenemases from multiple molecular classes that are responsible for resistance to almost all beta-lactams, including the carbapenems. Important plasmid-encoded carbapenemases include (a) the KPC beta-lactamases originating in Klebsiella pneumoniae isolates and now appearing worldwide in pan-resistant Gram-negative pathogens and (b) metallo-beta-lactamases that are produced in organisms with other deleterious beta-lactamases, causing resistance to all beta-lactams except aztreonam. beta-Lactamase genes encoding these enzymes are often carried on plasmids that bear additional resistance determinants for other antibiotic classes. As a result, some infections caused by Gram-negative pathogens can now be treated with only a limited number, if any, antibiotics. Because multidrug resistance in Gram-negative bacteria is observed in both nosocomial and community isolates, eradication of these resistant strains is becoming more difficult. | 2010 | 20594363 |