# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4837 | 0 | 1.0000 | Role of SHV-11, a Class A β-Lactamase, Gene in Multidrug Resistance Among Klebsiella pneumoniae Strains and Understanding Its Mechanism by Gene Network Analysis. Aim: The rapid emergence of β-lactam resistance in gram-negative bacteria is a major problem in the treatment of infections caused by pathogenic bacterial strains, in particular Klebsiella pneumoniae. In our study, we are presenting a systems biology approach to understand the role of SHV-11 gene in drug resistance mechanism patterns in K. pneumoniae strain. Results: From the results, we have observed that the SHV-11 gene has a role in drug resistance mechanism along with its functional partner genes gyrA, parC, glsA, osmE, yjhA, yhdT, rimL, pepB, KPN_00437, and KPN_01875. We have also observed that of 51 genes, 27 genes were enriched in various Gene Ontology terms such as DNA metabolic process, DNA repair, and response to stress. The genes gyrA, parC, gyrB, parE, recA, dnaA, polB, dnaK, mutS, and dnaN constitute >41% of the total interactions; thus, these genes can be considered as hub nodes in the network, and they can be used as the potential drug targets. Conclusions: Drug exposure leads to the DNA damage in bacterial spp. We observed that the SHV11 gene along with the functional partners help in maintaining the genomic integrity by withstanding the environmental stress by inducing DNA damage repair mechanism. Our results provide a detailed understanding on the role of SHV-11 gene in drug resistance mechanisms in K. pneumoniae, and we are of the opinion that our results will be useful for researchers exploring the antibiotic resistance mechanisms in pathogenic bacteria. | 2020 | 32119601 |
| 4627 | 1 | 0.9997 | Antibiotic resistance mechanisms of Myroides sp. Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria. | 2016 | 26984839 |
| 4875 | 2 | 0.9996 | An 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. | 2025 | 40078264 |
| 4820 | 3 | 0.9996 | Network Integrative Genomic and Transcriptomic Analysis of Carbapenem-Resistant Klebsiella pneumoniae Strains Identifies Genes for Antibiotic Resistance and Virulence. Global increases in the use of carbapenems have resulted in several strains of Gram-negative bacteria acquiring carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is a common carbapenem-resistant pathogenic bacterium that is widely studied to identify novel antibiotic resistance mechanisms and drug targets. Antibiotic-resistant clinical isolates generally harbor many genetic alterations, and the identification of responsible mutations would provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance on the basis of expression changes in their local subnetworks, hypothesizing that mutated genes that show significant expression changes among the corresponding functionally associated genes are more likely to be involved in the carbapenem resistance. For network-based gene prioritization, we developed KlebNet (www.inetbio.org/klebnet), a genome-scale cofunctional network of K. pneumoniae genes. Using KlebNet, we reconstructed the functional modules for carbapenem resistance and virulence and identified the functional association between antibiotic resistance and virulence. Using complementation assays with the top candidate genes, we were able to validate a novel gene that negatively regulated carbapenem resistance and four novel genes that positively regulated virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antibiotic resistance and virulence of human-pathogenic bacteria.IMPORTANCE Klebsiella pneumoniae is a major bacterial pathogen that causes pneumonia and urinary tract infections in human. K. pneumoniae infections are treated with carbapenem, but carbapenem-resistant K. pneumoniae has been spreading worldwide. We are able to identify antimicrobial-resistant genes among mutated genes of the antibiotic-resistant clinical isolates. However, they usually harbor many mutated genes, including those that cause weak or neutral functional effects. Therefore, we need to prioritize the mutated genes to identify the more likely candidates for the follow-up functional analysis. For this study, we present a functional network of K. pneumoniae genes and propose a network-based method of prioritizing the mutated genes of the resistant clinical isolates. We also reconstructed the network-based functional modules for carbapenem resistance and virulence and retrieved the functional association between antibiotic resistance and virulence. This study demonstrated the feasibility of network-based analysis of clinical genomics data for the study of K. pneumoniae infection. | 2019 | 31117026 |
| 4825 | 4 | 0.9996 | Proof of the triple prerequisite conditions which are essential for carbapenem resistance development in Klebsiella pneumoniae by using radiation-mediated mutagenesis. Evolution of multi-drug resistant bacteria has led to worldwide research to better understand the various resistance mechanisms in these strains. Every year, novel information on carbapenem resistance and its mechanisms is being discovered. In this study, radiation-mediated mutagenesis was used to transform a carbapenem-resistant Klebsiella pneumoniae strain to a carbapenem-susceptible bacterium. Through this process, we proved three conditions of loss of the OmpK35 and the OmpK36 genes and acquisition of blaCMY-10 worked together to produce carbapenem resistance in K. pneumoniae. Loss of only one of the porins did not evoke carbapenem resistance. This is the first report on the essential contribution of these three components of carbapenem resistance in K. pneumoniae. | 2021 | 33469646 |
| 4817 | 5 | 0.9996 | Relationship Between Biofilm Formation and Antimicrobial Resistance in Gram-Negative Bacteria. Gram-negative microorganisms are a significant cause of infection in both community and nosocomial settings. The increase, emergence, and spread of antimicrobial resistance among bacteria are the most important health problems worldwide. One of the mechanisms of resistance used by bacteria is biofilm formation, which is also a mechanism of virulence. This study analyzed the possible relationship between antimicrobial resistance and biofilm formation among isolates of three Gram-negative bacteria species. Several relationships were found between the ability to form biofilm and antimicrobial resistance, being different for each species. Indeed, gentamicin and ceftazidime resistance was related to biofilm formation in Escherichia coli, piperacillin/tazobactam, and colistin in Klebsiella pneumoniae, and ciprofloxacin in Pseudomonas aeruginosa. However, no relationship was observed between global resistance or multidrug-resistance and biofilm formation. In addition, compared with other reported data, the isolates in the present study showed higher rates of antimicrobial resistance. In conclusion, the acquisition of specific antimicrobial resistance can compromise or enhance biofilm formation in several species of Gram-negative bacteria. However, multidrug-resistant isolates do not show a trend to being greater biofilm producers than non-multiresistant isolates. | 2019 | 30142035 |
| 9909 | 6 | 0.9996 | Enterobacter aerogenes and Enterobacter cloacae; versatile bacterial pathogens confronting antibiotic treatment. Enterobacter aerogenes and E. cloacae have been reported as important opportunistic and multiresistant bacterial pathogens for humans during the last three decades in hospital wards. These Gram-negative bacteria have been largely described during several outbreaks of hospital-acquired infections in Europe and particularly in France. The dissemination of Enterobacter sp. is associated with the presence of redundant regulatory cascades that efficiently control the membrane permeability ensuring the bacterial protection and the expression of detoxifying enzymes involved in antibiotic degradation/inactivation. In addition, these bacterial species are able to acquire numerous genetic mobile elements that strongly contribute to antibiotic resistance. Moreover, this particular fitness help them to colonize several environments and hosts and rapidly and efficiently adapt their metabolism and physiology to external conditions and environmental stresses. Enterobacter is a versatile bacterium able to promptly respond to the antibiotic treatment in the colonized patient. The balance of the prevalence, E. aerogenes versus E. cloacae, in the reported hospital infections during the last period, questions about the horizontal transmission of mobile elements containing antibiotic resistance genes, e.g., the efficacy of the exchange of resistance genes Klebsiella pneumoniae to Enterobacter sp. It is also important to mention the possible role of antibiotic use in the treatment of bacterial infectious diseases in this E. aerogenes/E. cloacae evolution. | 2015 | 26042091 |
| 6279 | 7 | 0.9996 | Comparative transcriptomics analyses of the different growth states of multidrug-resistant Acinetobacter baumannii. Multidrug-resistant (MDR) Acinetobacter baumannii is an important bacterial pathogen commonly associated with hospital acquired infections. A. baumannii can remain viable and hence virulent in the environment for a long period of time due primarily to its ability to form biofilms. A total of 459 cases of MDR A. baumannii our hospital collected from March 2014 to March 2015 were examined in this study, and a representative isolate selected for high-throughput mRNA sequencing and comparison of gene expression profiles under the biofilm and exponential growth conditions. Our study found that the same bacteria indeed exhibited differential mRNA expression under different conditions. Compared to the rapidly growing bacteria, biofilm bacteria had 106 genes upregulated and 92 genes downregulated. Bioinformatics analyses suggested that many of these genes are involved in the formation and maintenance of biofilms, whose expression also depends on the environment and specific signaling pathways and transcription factors that are absent in the log phase bacteria. These differentially expressed mRNAs might contribute to A. baumannii's unique pathogenicity and ability to inflict chronic and recurrent infections. | 2017 | 27916419 |
| 4628 | 8 | 0.9996 | Genomic Analysis of Molecular Bacterial Mechanisms of Resistance to Phage Infection. To optimize phage therapy, we need to understand how bacteria evolve against phage attacks. One of the main problems of phage therapy is the appearance of bacterial resistance variants. The use of genomics to track antimicrobial resistance is increasingly developed and used in clinical laboratories. For that reason, it is important to consider, in an emerging future with phage therapy, to detect and avoid phage-resistant strains that can be overcome by the analysis of metadata provided by whole-genome sequencing. Here, we identified genes associated with phage resistance in 18 Acinetobacter baumannii clinical strains belonging to the ST-2 clonal complex during a decade (Ab2000 vs. 2010): 9 from 2000 to 9 from 2010. The presence of genes putatively associated with phage resistance was detected. Genes detected were associated with an abortive infection system, restriction-modification system, genes predicted to be associated with defense systems but with unknown function, and CRISPR-Cas system. Between 118 and 171 genes were found in the 18 clinical strains. On average, 26% of these genes were detected inside genomic islands in the 2000 strains and 32% in the 2010 strains. Furthermore, 38 potential CRISPR arrays in 17 of 18 of the strains were found, as well as 705 proteins associated with CRISPR-Cas systems. A moderately higher presence of these genes in the strains of 2010 in comparison with those of 2000 was found, especially those related to the restriction-modification system and CRISPR-Cas system. The presence of these genes in genomic islands at a higher rate in the strains of 2010 compared with those of 2000 was also detected. Whole-genome sequencing and bioinformatics could be powerful tools to avoid drawbacks when a personalized therapy is applied. In this study, it allows us to take care of the phage resistance in A. baumannii clinical strains to prevent a failure in possible phage therapy. | 2021 | 35250902 |
| 4625 | 9 | 0.9996 | Resistome analysis of bloodstream infection bacterial genomes reveals a specific set of proteins involved in antibiotic resistance and drug efflux. Bacterial resistance to antibiotics is a global public health problem. Its association with bloodstream infections is even more severe and may easily evolve to sepsis. To improve our response to these bacteria, it is essential to gather thorough knowledge on the main pathogens along with the main mechanisms of resistance they carry. In this paper, we performed a large meta-analysis of 3872 bacterial genomes isolated from blood samples, from which we identified 71 745 antibiotic resistance genes (ARGs). Taxonomic analysis showed that Proteobacteria and Firmicutes phyla, and the species Klebsiella pneumoniae and Staphylococcus aureus were the most represented. Comparison of ARGs with the Resfams database showed that the main mechanism of antibiotic resistance is mediated by efflux pumps. Clustering analysis between resistome of blood and soil-isolated bacteria showed that there is low identity between transport and efflux proteins between bacteria from these environments. Furthermore, a correlation analysis among all features showed that K. pneumoniae and S. aureus formed two well-defined clusters related to the resistance mechanisms, proteins and antibiotics. A retrospective analysis has shown that the average number of ARGs per genome has gradually increased. The results demonstrate the importance of comprehensive studies to understand the antibiotic resistance phenomenon. | 2020 | 33575606 |
| 4839 | 10 | 0.9996 | beta-Lactamases: protein evolution in real time. The evolution and spread of bacteria resistant to beta-lactam antibiotics has progressed at an alarming rate. Bacteria may acquire resistance to a given drug by mutation of pre-existing genes or by the acquisition of new genes from other bacteria. One ongoing example of these mechanisms is the evolution of new variants of the TEM and SHV beta-lactamases with altered substrate specificity. | 1998 | 9746943 |
| 6267 | 11 | 0.9996 | Beta-lactamase dependent and independent evolutionary paths to high-level ampicillin resistance. The incidence of beta-lactam resistance among clinical isolates is a major health concern. A key method to study the emergence of antibiotic resistance is adaptive laboratory evolution. However, in the case of the beta-lactam ampicillin, bacteria evolved in laboratory settings do not recapitulate clinical-like resistance levels, hindering efforts to identify major evolutionary paths and their dependency on genetic background. Here, we used the Microbial Evolution and Growth Arena (MEGA) plate to select ampicillin-resistant Escherichia coli mutants with varying degrees of resistance. Whole-genome sequencing of resistant isolates revealed that ampicillin resistance was acquired via a combination of single-point mutations and amplification of the gene encoding beta-lactamase AmpC. However, blocking AmpC-mediated resistance revealed latent adaptive pathways: strains deleted for ampC were able to adapt through combinations of changes in genes involved in multidrug resistance encoding efflux pumps, transcriptional regulators, and porins. Our results reveal that combinations of distinct genetic mutations, accessible at large population sizes, can drive high-level resistance to ampicillin even independently of beta-lactamases. | 2024 | 38918379 |
| 4840 | 12 | 0.9996 | Beta-lactam antibiotics and selection of resistance: speculation on the evolution of R-plasmids. In this paper we describe two genetic mechanisms which are responsible for the development of resistance to third-generation cephalosporins. One is a plasmid-mediated mechanism involving a mutation in the SHV-1-gene towards the production of the beta-lactamase SHV-2 which has increased affinity for these antibiotics. The other is chromosomally mediated and occurs at high frequency by mutation of inducible beta-lactamase-genes, leading to derepressed production of the enzyme. Together with other examples of resistance genes these two mechanisms lead us to a hypothesis about the evolution of beta-lactamase producing bacteria. | 1986 | 3542929 |
| 4829 | 13 | 0.9996 | Diversity of the mechanisms of resistance to beta-lactam antibiotics. The sensitivity of a bacterium to beta-lactam antibiotics depends upon the interplay between 3 independent factors: the sensitivity of the essential penicillin-binding enzyme(s), the quantity and properties of the beta-lactamase(s) and the diffusion barrier that the outer-membrane of Gram-negative bacteria can represent. Those three factors can be modified by mutations or by the horizontal transfer of genes or portions of genes. | 1991 | 1961980 |
| 9910 | 14 | 0.9996 | Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-Negatives: the Klebsiella pneumoniae Paradigm. Plasmids harbor genes coding for specific functions including virulence factors and antibiotic resistance that permit bacteria to survive the hostile environment found in the host and resist treatment. Together with other genetic elements such as integrons and transposons, and using a variety of mechanisms, plasmids participate in the dissemination of these traits, resulting in the virtual elimination of barriers among different kinds of bacteria. In this article we review the current information about the physiology of plasmids and their role in virulence and antibiotic resistance from the Gram-negative opportunistic pathogen Klebsiella pneumoniae. This bacterium has acquired multidrug resistance and is the causative agent of serious community- and hospital-acquired infections. It is also included in the recently defined ESKAPE group of bacteria that cause most U.S. hospital infections. | 2014 | 26104358 |
| 4844 | 15 | 0.9996 | Genetic basis of molecular mechanisms in β-lactam resistant gram-negative bacteria. Antibiotic-resistant bacteria are considered one of the major global threats to human and animal health. The most harmful among the resistant bacteria are β-lactamase producing Gram-negative species (β-lactamases). β-lactamases constitute a paradigm shift in the evolution of antibiotic resistance. Therefore, it is imperative to present a comprehensive review of the mechanisms responsible for developing antimicrobial resistance. Resistance due to β-lactamases develops through a variety of mechanisms, and the number of resistant genes are involved that can be transferred between bacteria, mostly via plasmids. Over time, these new molecular-based resistance mechanisms have been progressively disclosed. The present review article provides information on the recent findings regarding the molecular mechanisms of resistance to β-lactams in Gram-negative bacteria, including CTX-M-type ESBLs with methylase activity, plasmids harbouring phages with β-lactam resistance genes, the co-presence of β-lactam resistant genes of unique combinations and the presence of β-lactam and non-β-lactam antibiotic-resistant genes in the same bacteria. Keeping in view, the molecular level resistance development, multifactorial and coordinated measures may be taken to counter the challenge of rapidly increasing β-lactam resistance. | 2021 | 34119627 |
| 4380 | 16 | 0.9996 | Comparative genome analysis of ciprofloxacin-resistant Pseudomonas aeruginosa reveals genes within newly identified high variability regions associated with drug resistance development. The alarming rise of ciprofloxacin-resistant Pseudomonas aeruginosa has been reported in several clinical studies. Though the mutation of resistance genes and their role in drug resistance has been researched, the process by which the bacterium acquires high-level resistance is still not well understood. How does the genomic evolution of P. aeruginosa affect resistance development? Could the exposure of antibiotics to the bacteria enrich genomic variants that lead to the development of resistance, and if so, how are these variants distributed through the genome? To answer these questions, we performed 454 pyrosequencing and a whole genome analysis both before and after exposure to ciprofloxacin. The comparative sequence data revealed 93 unique resistance strain variation sites, which included a mutation in the DNA gyrase subunit A gene. We generated variation-distribution maps comparing the wild and resistant types, and isolated 19 candidates from three discrete resistance-associated high variability regions that had available transposon mutants, to perform a ciprofloxacin exposure assay. Of these region candidates with transposon disruptions, 79% (15/19) showed a reduction in the ability to gain high-level resistance, suggesting that genes within these high variability regions might enrich for certain functions associated with resistance development. | 2013 | 23808957 |
| 4569 | 17 | 0.9996 | Effect of oxygen on antimicrobial resistance genes from a one health perspective. Bacteria must face and adapt to a variety of physicochemical conditions in the environment and during infection. A key condition is the concentration of dissolved oxygen, proportional to the partial pressure of oxygen (PO(2)), which is extremely variable among environmental biogeographical areas and also compartments of the human and animal body. Here, we sought to understand if the phenotype of resistance determinants commonly found in Enterobacterales can be influenced by oxygen pressure. To do so, we have compared the MIC in aerobic and anaerobic conditions of isogenic Escherichia coli strains containing 136 different resistance genes against 8 antibiotic families. Our results show a complex landscape of changes in the performance of resistance genes in anaerobiosis. Certain changes are especially relevant for their intensity and the importance of the antibiotic family, like the large decreases in resistance observed against ertapenem and fosfomycin among bla(VIM) β-lactamases and certain fos genes, respectively; however, the bla(OXA-48) β-lactamase from the clinically relevant pOXA-48 plasmid conferred 4-fold higher ertapenem resistance in anaerobiosis. Strong changes in resistance patterns in anaerobiosis were also conserved in Klebsiella pneumoniae. Our results suggest that anaerobiosis is a relevant aspect that can affect the action and selective power of antibiotics for specific AMRs in different environments. | 2025 | 40286623 |
| 4860 | 18 | 0.9996 | The 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. | 2013 | 22894617 |
| 3808 | 19 | 0.9996 | Expression Profiling of Antibiotic-Resistant Bacteria Obtained by Laboratory Evolution. To elucidate the mechanisms of antibiotic resistance, integrating phenotypic and genotypic features in resistant strains is important. Here, we describe the expression profiling of antibiotic-resistant Escherichia coli strains obtained by laboratory evolution, and a method for extracting a small number of genes whose expression changes can contribute to the acquisition of resistance. | 2017 | 27873258 |