Molecular mechanisms related to colistin resistance in Enterobacteriaceae. - Related Documents




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486501.0000Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.201931190901
486611.0000Resistance to polymyxins in Gram-negative organisms. Polymyxins have recently been re-introduced into the therapeutic arsenal to combat infections caused by multidrug-resistant Gram-negative bacteria. However, the emergence of strains resistant to these last-resort drugs is becoming a critical issue in a growing number of countries. Both intrinsic and transferable mechanisms of polymyxin resistance have been characterised. These mechanisms as well as the epidemiological data regarding four relevant bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) are considered in this review. A special focus is made on plasmid-mediated resistance and the spread of mcr genes.201728163137
486420.9999Colistin resistance mechanisms in Gram-negative bacteria: a Focus on Escherichia coli. Multidrug-resistant (MDR) Escherichia coli strains have rapidly increased worldwide, and effective antibiotic therapeutic options are becoming more restricted. As a polymyxin antibiotic, colistin has a long history of usage, and it is used as a final line of treatment for severe infections by Gram-negative bacteria (GNB) with high-level resistance. However, its application has been challenged by the emergence of E. coli colistin resistance. Hence, determining the mechanism that confers colistin resistance is crucial for monitoring and controlling the dissemination of colistin-resistant E. coli strains. This comprehensive review summarizes colistin resistance mechanisms in E. coli strains and concentrates on the history, mode of action, and therapeutic implications of colistin. We have mainly focused on the fundamental mechanisms of colistin resistance that are mediated by chromosomal or plasmid elements and discussed major mutations in the two-component systems (TCSs) genes and plasmids that transmit the mobilized colistin resistance resistant genes in E. coli strains.202336754367
486230.9999Genetic Factors That Contribute to Antibiotic Resistance through Intrinsic and Acquired Bacterial Genes in Urinary Tract Infections. The overprescribing and misuse of antibiotics have led to the rapid development of multidrug-resistant bacteria, such as those that cause UTIs. UTIs are the most common outpatient infections and are mainly caused by Escherichia coli and Klebsiella spp., although some Gram-positive bacteria, such as Pseudomonas aeruginosa, have been isolated in many cases. The rise of antimicrobial-resistant bacteria is a major public health concern, as it is predicted to lead to increased healthcare costs and poor patient outcomes and is expected to be the leading cause of global mortality by 2050. Antibiotic resistance among bacterial species can arise from a myriad of factors, including intrinsic and acquired resistance mechanisms, as well as mobile genetic elements, such as transposons, integrons, and plasmids. Plasmid-mediated resistance is of major concern as drug-resistance genes can quickly and efficiently spread across bacterial species via horizontal gene transfer. The emergence of extended-spectrum β-lactamases (ESBLs) such as NDM-1, OXA, KPC, and CTX-M family members has conferred resistance to many commonly used antibiotics in the treatment of UTIs, including penicillins, carbapenems, cephalosporins, and sulfamethoxazole. This review will focus on plasmid-mediated bacterial genes, especially those that encode ESBLs, and how they contribute to antibiotic resistance. Early clinical detection of these genes in patient samples will provide better treatment options and reduce the threat of antibiotic resistance.202337374909
486840.9999Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria. Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.201322667455
486350.9999Carbapenem Resistance in Gram-Negative Bacteria: The Not-So-Little Problem in the Little Red Dot. Singapore is an international travel and medical hub and faces a genuine threat for import and dissemination of bacteria with broad-spectrum resistance. In this review, we described the current landscape and management of carbapenem resistance in Gram-negative bacteria (GNB) in Singapore. Notably, the number of carbapenem-resistant Enterobacteriaceae has exponentially increased in the past two years. Resistance is largely mediated by a variety of mechanisms. Polymyxin resistance has also emerged. Interestingly, two Escherichia coli isolates with plasmid-mediated mcr-1 genes have been detected. Evidently, surveillance and infection control becomes critical in the local setting where resistance is commonly related to plasmid-mediated mechanisms, such as carbapenemases. Combination antibiotic therapy has been proposed as a last-resort strategy in the treatment of extensively drug-resistant (XDR) GNB infections, and is widely adopted in Singapore. The diversity of carbapenemases encountered, however, presents complexities in both carbapenemase detection and the selection of optimal antibiotic combinations. One unique strategy introduced in Singapore is a prospective in vitro combination testing service, which aids physicians in the selection of individualized combinations. The outcome of this treatment strategy has been promising. Unlike countries with a predominant carbapenemase type, Singapore has to adopt management strategies which accounts for diversity in resistance mechanisms.201627681907
482360.9999A Review of Resistance to Polymyxins and Evolving Mobile Colistin Resistance Gene (mcr) among Pathogens of Clinical Significance. The global rise in antibiotic resistance in bacteria poses a major challenge in treating infectious diseases. Polymyxins (e.g., polymyxin B and colistin) are last-resort antibiotics against resistant Gram-negative bacteria, but the effectiveness of polymyxins is decreasing due to widespread resistance among clinical isolates. The aim of this literature review was to decipher the evolving mechanisms of resistance to polymyxins among pathogens of clinical significance. We deciphered the molecular determinants of polymyxin resistance, including distinct intrinsic molecular pathways of resistance as well as evolutionary characteristics of mobile colistin resistance. Among clinical isolates, Acinetobacter stains represent a diversified evolution of resistance, with distinct molecular mechanisms of intrinsic resistance including naxD, lpxACD, and stkR gene deletion. On the other hand, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are usually resistant via the PhoP-PhoQ and PmrA-PmrB pathways. Molecular evolutionary analysis of mcr genes was undertaken to show relative relatedness across the ten main lineages. Understanding the molecular determinants of resistance to polymyxins may help develop suitable and effective methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules.202337998799
486170.9999The Challenge of Global Emergence of Novel Colistin-Resistant Escherichia coli ST131. Escherichia coli ST131 is one of the high-risk multidrug-resistant clones with a global distribution and the ability to persist and colonize in a variety of niches. Carbapenemase-producing E. coli ST131 strains with the ability to resist last-line antibiotics (i.e., colistin) have been recently considered a significant public health. Colistin is widely used in veterinary medicine and therefore, colistin-resistant bacteria can be transmitted from livestock to humans through food. There are several mechanisms of resistance to colistin, which include chromosomal mutations and plasmid-transmitted mcr genes. E. coli ST131 is a great model organism to investigate the emergence of superbugs. This microorganism has the ability to cause intestinal and extraintestinal infections, and its accurate identification as well as its antibiotic resistance patterns are vitally important for a successful treatment strategy. Therefore, further studies are required to understand the evolution of this resistant organism for drug design, controlling the evolution of other nascent emerging pathogens, and developing antibiotic stewardship programs. In this review, we will discuss the importance of E. coli ST131, the mechanisms of resistance to colistin as the last-resort antibiotic against resistant Gram-negative bacteria, reports from different regions regarding E. coli ST131 resistance to colistin, and the most recent therapeutic approaches against colistin-resistance bacteria.202133913748
485980.9999Nosocomial infection and its molecular mechanisms of antibiotic resistance. Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.201626877142
502590.9999An Update of Mobile Colistin Resistance in Non-Fermentative Gram-Negative Bacilli. Colistin, the last resort for multidrug and extensively drug-resistant bacterial infection treatment, was reintroduced after being avoided in clinical settings from the 1970s to the 1990s because of its high toxicity. Colistin is considered a crucial treatment option for Acinetobacter baumannii and Pseudomonas aeruginosa, which are listed as critical priority pathogens for new antibiotics by the World Health Organization. The resistance mechanisms of colistin are considered to be chromosomally encoded, and no horizontal transfer has been reported. Nevertheless, in November 2015, a transmissible resistance mechanism of colistin, called mobile colistin resistance (MCR), was discovered. Up to ten families with MCR and more than 100 variants of Gram-negative bacteria have been reported worldwide. Even though few have been reported from Acinetobacter spp. and Pseudomonas spp., it is important to closely monitor the epidemiology of mcr genes in these pathogens. Therefore, this review focuses on the most recent update on colistin resistance and the epidemiology of mcr genes among non-fermentative Gram-negative bacilli, especially Acinetobacter spp. and P. aeruginosa.202235782127
4822100.9999A Molecular Perspective on Colistin and Klebsiella pneumoniae: Mode of Action, Resistance Genetics, and Phenotypic Susceptibility. Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae.202134202395
4860110.9999The rise of carbapenem-resistant Acinetobacter baumannii. Acinetobacter spp. are Gram-negative bacteria that have become one of the most difficult pathogens to treat. The species A. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. It is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating Gram-negative bacteria, including the fluoroquinolones and the cephalosporins. Some members of the species have accumulated these resistance genes in large resistance islands, located in a "hot-spot" within the bacterial chromosome. The only conventional remaining treatment options were the carbapenems. However, A. baumannii possesses an inherent class D β-lactamase gene (blaOXA-51-like) that can have the ability to confer carbapenem resistance. Additionally, mechanisms of carbapenem resistance have emerged that derive from the importation of the distantly related class D β-lactamase genes blaOXA-23 and blaOXA-58. Although not inducible, the expression of these genes is controlled by mobile promoters carried on ISAba elements. It has also been found that other resistance genes including the chromosomal class C β-lactamase genes conferring cephalosporin resistance are controlled in the same manner. Colistin is now considered to be the final drug capable of treating infections caused by carbapenem-resistant A. baumannii; however, strains are now being isolated that are resistant to this antibiotic as well. The increasing inability to treat infections caused by A. baumannii ensures that this pathogen more than ranks with MRSA or Clostridium difficile as a threat to modern medicine.201322894617
4870120.9999Emergent Polymyxin Resistance: End of an Era? Until recently, the polymyxin antibiotics were sparingly used due to dose limiting toxicities. However, the lack of therapeutic alternatives for infections caused by highly resistant Gram-negative bacteria has led to the increased use of the polymyxins. Unfortunately, in the last decade the world has witnessed increased rates of polymyxin resistance, which is likely in part due to its irrational use in human and veterinary medicine. The spread of polymyxin-resistance has been aided by the dissemination of the transferable polymyxin-resistance gene, mcr, in humans and the environment. The mortality of colistin-resistant bacteria infections varies in different reports. However, poor clinical outcome was associated with prior colistin treatment, illness severity, complications and multidrug resistance. Detection of polymyxin-resistance in the clinic is possible through multiple robust and practical tests including broth microdilution susceptibility testing, chromogenic agar testing, and molecular biology assays. There are multiple risk factors that increase a person's risk for infection with a polymyxin-resistant bacteria including age, prior colistin treatment, hospitalization and ventilator support. For patients that are determined to be infected by polymyxin-resistant bacteria, various antibiotic treatment options currently exist. The rising trend of polymyxin-resistance threatens patient care and warrants an effective control.201931420655
4857130.9999The emergence of bacterial resistance and its influence on empiric therapy. The discovery of antimicrobial agents had a major impact on the rate of survival from infections. However, the changing patterns of antimicrobial resistance caused a demand for new antibacterial agents. Within a few years of the introduction of penicillin, the majority of staphylococci were resistant to that drug. In the 1960s the production of the semisynthetic penicillins provided an answer to the problem of staphylococcal resistance. In the early 1960s most Escherichia coli were susceptible to the new beta-lactam antibiotic ampicillin; by the end of that decade, plasmid-mediated beta-lactamase resistance was found in 30%-50% of hospital-acquired E. coli. Use of certain agents resulted in the selection of bacteria, such as Klebsiella, that are intrinsically resistant to ampicillin. The original cephalosporins were stable to beta-lactamase, but the use of these agents was in part responsible for the appearance of infections due to Enterobacter species, Citrobacter species, and Pseudomonas aeruginosa. These bacteria, as well as Serratia, were resistant to many of the available beta-lactam agents. Aminoglycosides initially provided excellent activity against most of the facultative gram-negative bacteria. However, the widespread dissemination of the genes that cause production of the aminoglycoside-inactivating enzymes altered the use of those agents. Clearly, the evolution of bacterial resistance has altered the prescribing patterns for antimicrobial agents. Knowledge that beta-lactam resistance to ampicillin or cephalothin is prevalent is causing physicians to select as empiric therapy either a combination of two or more agents or agents to which resistance is uncommon. The new cephalosporins offer a broad spectrum of anti-bacterial activity coupled with low toxicity. However, physicians must closely follow the changing ecology of bacteria when these agents are used, because cephalosporins can also select bacteria resistant to themselves and thereby abolish their value as empiric therapy.19836342103
4854140.9999Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria. Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.201931724045
4867150.9999Metallo Beta Lactamase Enzymes. Multidrug resistance has become more common in Gram-negative bacteria, making them one of the emerging public health problems with extremely detrimental effects on the world economy. These drugs are broad-spectrum-lactam antibiotics used as a last-resort treatment against multidrug-resistant microorganisms (MDROs). As the resistance to these last-line drugs grows, so does the need to detect and deal with MDROs that carbapenem-resistant. The group B carbapenemases, such as Imipenem metallo-lactamases (IMP) and Verona integron-encoded metallo-lactamases (VIM), are the most prevalent. Integrons, which also include various antibiotic resistance genes, contain the genes for IMP and VIM, promoting their worldwide proliferation. Many papers reported that spreading genes of these enzymes among bacteria rapidly nowadays had had a negative effect on infection control. This review can help with ensuring the understanding of carbapenem resistance as well as policies for eradications and declination of resistance mechanisms that are critical not only for therapeutic treatment but also for infection control measures and epidemic investigations and detections. This review aims to comprehend the mechanism of resistance and transmission of these elements.202540655350
4875160.9999An Overview of the Genetic Mechanisms of Colistin-Resistance in Bacterial Pathogens: An Indian Perspective. Colistin resistance in bacteria is a growing global issue, given its role as a critical last-resort antibiotic, particularly for treating Gram-negative bacterial infections. Pathogens adopt multiple resistance mechanisms, mediated either by plasmids or chromosomal changes. Some of the most frequently observed strategies include the occurrence of plasmid-borne mobile colistin resistance (mcr) genes, enhanced efflux pump activity, mutations in the regulatory systems, and alterations in the lipid A structure. This article provides an overview of the studies investigating the genetic mechanisms underlying colistin resistance in nosocomial Gram-negative bacteria from India. A total of 37 studies were identified through online searches across various databases, including PubMed, ScienceDirect, and Web of Science. These studies were reviewed to examine bacterial species and their mechanisms of colistin resistance. Over 26 (70.27%) studies were focused on Klebsiella pneumoniae. The most commonly reported mechanism of colistin resistance involved mutations in the two-component systems pmrAB and phoPQ. Plasmid-mediated colistin-resistant mcr genes were identified in 22 studies (18.18%). Four studies reported the overexpression of efflux pump genes as a mechanism of colistin resistance. This article provides a comprehensive summary of these studies, emphasizing the presence of diverse resistance mechanisms across various pathogens. It underscores the necessity for future genomic research on a broader range of pathogens to investigate the prevalence of different mechanisms of colistin resistance in the various regions of India.202540078264
4881170.9998Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics. Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.201931354944
9791180.9998Beta-lactam resistance and the effectiveness of antimicrobial peptides against KPC-producing bacteria. Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta-lactams and explicitly explain the activity of AMPs against carbapenemase-producing bacteria as potential alternative agents for infection control.202236042694
5028190.9998The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria. Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups.202032316342