COLIBACTIN - Word Related Documents




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827700.9679The bacterial toxin colibactin triggers prophage induction. Colibactin is a chemically unstable small-molecule genotoxin that is produced by several different bacteria, including members of the human gut microbiome(1,2). Although the biological activity of colibactin has been extensively investigated in mammalian systems(3), little is known about its effects on other microorganisms. Here we show that colibactin targets bacteria that contain prophages, and induces lytic development through the bacterial SOS response. DNA, added exogenously, protects bacteria from colibactin, as does expressing a colibactin resistance protein (ClbS) in non-colibactin-producing cells. The prophage-inducing effects that we observe apply broadly across different phage-bacteria systems and in complex communities. Finally, we identify bacteria that have colibactin resistance genes but lack colibactin biosynthetic genes. Many of these bacteria are infected with predicted prophages, and we show that the expression of their ClbS homologues provides immunity from colibactin-triggered induction. Our study reveals a mechanism by which colibactin production could affect microbiomes and highlights a role for microbial natural products in influencing population-level events such as phage outbreaks.202235197633
490010.9661Study on the antibacterial effect of CuO nanoparticles on Klebsiella pneumonia bacteria: Efficient treatment for colorectal cancer. Colorectal cancer (CRC) is a widespread type of cancer across the world. One efficient therapy approach is the use of antibiotic agents, but one of the main issues related to treating CRC is microbial resistance to antibiotics. As microbes are becoming more resistant to antibiotics and other traditional antimicrobial agents, nanobiotechnology has made it possible to employ nanomaterials with the aim of creating a new generation of antimicrobial agents. In the present study, we have assessed the antimicrobial potential of CuO nanoparticles (NPs) against gram-negative bacteria like Klebsiella pneumoniae carrying PKS genes responsible for encoding colibactin as the key factor for CRC development. For this purpose, the antibacterial effects of conventional antibacterial agents, including erythromycin, piperacillin, and ampicillin, as well as CuONPs, were compared on isolated strains from cancerous candidates. The obtained results revealed that isolates (K. pneumoniae) showed resistance toward the mentioned conventional antibiotics, but CuONPs showed efficient antibacterial properties against K. pneumonia with a MIC = 62 μg/mL. On the other hand, a synergistic antibacterial effect was obtained when CuONPs were used in combination with conventional antibiotics, which are ineffective when used alone. Therefore, CuONPs can be introduced as an excellent antimicrobial agent against K. pneumoniae bacteria in CRC, especially when they are combined with other antibiotics since they can activate the antimicrobial activity of the conventional antibiotics.202337264727
249320.9660Multidrug-resistant hypervirulent Klebsiella pneumoniae: an evolving superbug. Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) combines high pathogenicity with multidrug resistance to become a new superbug. MDR-hvKP reports continue to emerge, shattering the perception that hypervirulent K. pneumoniae (hvKP) strains are antibiotic sensitive. Patients infected with MDR-hvKP strains have been reported in Asia, particularly China. Although hvKP can acquire drug resistance genes, MDR-hvKP seems to be more easily transformed from classical K. pneumoniae (cKP), which has a strong gene uptake ability. To better understand the biology of MDR-hvKP, this review discusses the virulence factors, resistance mechanisms, formation pathways, and identification of MDR-hvKP. Given their destructive and transmissible potential, continued surveillance of these organisms and enhanced control measures should be prioritized.202540135944
978530.9658Mis-annotations of a promising antibiotic target in high-priority gram-negative pathogens. The rise of antibiotic resistance combined with the lack of new products entering the market has led to bacterial infections becoming one of the biggest threats to global health. Therefore, there is an urgent need to identify novel antibiotic targets, such as dihydrodipicolinate synthase (DHDPS), an enzyme involved in the production of essential metabolites in cell wall and protein synthesis. Here, we utilised a 7-residue sequence motif to identify mis-annotation of multiple DHDPS genes in the high-priority Gram-negative bacteria Acinetobacter baumannii and Klebsiella pneumoniae. We subsequently confirmed these mis-annotations using a combination of enzyme kinetics and X-ray crystallography. Thus, this study highlights the need to ensure genes encoding promising drug targets, like DHDPS, are annotated correctly, especially for clinically important pathogens. PDB ID: 6UE0.202031943170
588340.9655Genome-wide analysis reveals the emergence of multidrug resistant Stenotrophomonas acidaminiphila strain SINDOREI isolated from a patient with sepsis. Stenotrophomonas acidaminiphila, the most recent reported species in genus Stenotrophomonas, is a relatively rare bacteria and is an aerobic, glucose non-fermentative, Gram-negative bacterium. However, little information of S. acidaminiphila is known to cause human infections. In this research, we firstly reported a multidrug-resistant strain S. acidaminiphila SINDOREI isolated from the blood of a patient with sepsis, who was dead of infection eventually. The whole genome of strain SINDOREI was sequenced, and genome comparisons were performed among six closely related S. acidaminiphila strains. The core genes (2,506 genes) and strain-specific genes were identified, respectively, to know about the strain-level diversity in six S. acidaminiphila stains. The presence of a unique gene (narG) and essential genes involved in biofilm formation in strain SINDOREI are important for the pathogenesis of infections. Strain SINDOREI was resistant to trimethoprim/sulfamethoxazole, ciprofloxacin, ofloxacin, cefepime, ceftazidime, and aztreonam. Several common and specific antibiotic resistance genes were identified in strain SINDOREI. The presence of two sul genes and exclusive determinants GES-1, aadA3, qacL, and cmlA5 is responsible for the resistance to multidrug. The virulence factors and resistance determinants can show the relationship between the phenotype and genotype and afford potential therapeutic strategies for infections.202236212813
22750.9655Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins. The susceptibility of colistin-resistant clinical isolates of Klebsiella pneumoniae to ceragenins and antimicrobial peptides (AMPs) suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs and that lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. These results suggest that there are differences in the resistance mechanisms to colistin and ceragenins/AMPs.201728584137
444560.9654Genomic Analysis and Resistance Mechanisms in Shigella flexneri 2a Strain 301. Shigella flexneri is one of the most prominent pathogenic bacteria in developing countries. In the battle against shigellosis and other bacterial diseases, antibiotic resistance has become an increasing global public health threat. Although the serious phenomenon of multidrug resistance (MDR) has been identified as one of the top three burdens on human health, resistance mechanisms are still poorly understood at the molecular level. In this study, we analyzed genomic data and the evolution of resistance in Shigella flexneri under sequential selection stress from three separate antibiotics: ciprofloxacin (CIP), ceftriaxone (CRO), and tetracycline. Through whole-genome sequencing, 82 chromosomal antibiotic resistance genes were identified. Re-sequencing of the evolved populations identified single nucleotide polymorphisms (SNPs) that contributed to MDR and SNPs that were specific to a single drug. A total of 40 SNPs in 8 genes and 3 intergenic regions, including mutations in metG (L582R) and 1538924, 1538924, and 1538924, appeared under each antibiotic. Several nonsynonymous mutations in gyrB (S464Y), ydgA (E378A), rob (R156H), and narX (K75E) were observed under selective pressure from CIP or CRO. Based on a bioinformatic analysis and previous reports, we discuss the contribution of these mutated genes to resistance. Therefore, more circumspect selection and use of antimicrobial drugs for treating shigellosis is necessary.201828853989
612970.9654Yersinia ruckeri Infection and Enteric Redmouth Disease among Endangered Chinese Sturgeons, China, 2022. During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.202438781928
604580.9651Lacticaseicin 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.202135052897
20390.9649Evolution of insect innate immunity through domestication of bacterial toxins. Toxin cargo genes are often horizontally transferred by phages between bacterial species and are known to play an important role in the evolution of bacterial pathogenesis. Here, we show how these same genes have been horizontally transferred from phage or bacteria to animals and have resulted in novel adaptations. We discovered that two widespread bacterial genes encoding toxins of animal cells, cytolethal distending toxin subunit B (cdtB) and apoptosis-inducing protein of 56 kDa (aip56), were captured by insect genomes through horizontal gene transfer from bacteria or phages. To study the function of these genes in insects, we focused on Drosophila ananassae as a model. In the D. ananassae subgroup species, cdtB and aip56 are present as singular (cdtB) or fused copies (cdtB::aip56) on the second chromosome. We found that cdtB and aip56 genes and encoded proteins were expressed by immune cells, some proteins were localized to the wasp embryo's serosa, and their expression increased following parasitoid wasp infection. Species of the ananassae subgroup are highly resistant to parasitoid wasps, and we observed that D. ananassae lines carrying null mutations in cdtB and aip56 toxin genes were more susceptible to parasitoids than the wild type. We conclude that toxin cargo genes were captured by these insects millions of years ago and integrated as novel modules into their innate immune system. These modules now represent components of a heretofore undescribed defense response and are important for resistance to parasitoid wasps. Phage or bacterially derived eukaryotic toxin genes serve as macromutations that can spur the instantaneous evolution of novelty in animals.202337036995
799100.9648An ace up their sleeve: a transcriptomic approach exposes the AceI efflux protein of Acinetobacter baumannii and reveals the drug efflux potential hidden in many microbial pathogens. The era of antibiotics as a cure-all for bacterial infections appears to be coming to an end. The emergence of multidrug resistance in many hospital-associated pathogens has resulted in "superbugs" that are effectively untreatable. Multidrug efflux pumps are well known mediators of bacterial drug resistance. Genome sequencing efforts have highlighted an abundance of putative efflux pump genes in bacteria. However, it is not clear how many of these pumps play a role in antimicrobial resistance. Efflux pump genes that participate in drug resistance can be under tight regulatory control and expressed only in response to substrates. Consequently, changes in gene expression following antimicrobial shock may be used to identify efflux pumps that mediate antimicrobial resistance. Using this approach we have characterized several novel efflux pumps in bacteria. In one example we recently identified the Acinetobacterchlorhexidine efflux protein (AceI) efflux pump in Acinetobacter. AceI is a prototype for a novel family of multidrug efflux pumps conserved in many proteobacterial lineages. The discovery of this family raises the possibility that additional undiscovered intrinsic resistance proteins may be encoded in the core genomes of pathogenic bacteria.201525954261
9793110.9647Recent Review on Subclass B1 Metallo-β-lactamases Inhibitors: Sword for Antimicrobial Resistance. An emerging crisis of antibiotic resistance for microbial pathogens is alarming all the nations, posing a global threat to human health. The production of the metalloβ-lactamase enzyme is the most powerful strategy of bacteria to produce resistance. An efficient way to combat this global health threat is the development of broad/non-specific type of metalloβ-lactamase inhibitors, which can inhibit the different isoforms of the enzyme. Till date, there are no clinically active drugs against metallo- β-lactamase. The lack of efficient drug molecules against MBLs carrying bacteria requires continuous research efforts to overcome the problem of multidrug-resistance bacteria. The present review will discuss the clinically potent molecules against different variants of B1 metalloβ-lactamase.201930556502
4896120.9647The changing ecology of bacterial infections in children. There is continued change in the organisms involved in commonly encountered infections. Although the major organisms have changed less in pediatric than in medical or surgical infections, the advances in neonatology and the chemotherapy of leukemia have resulted in cases in which infection with once uncommon organisms is now commonplace. Perhaps more disheartening has been the increasing resistance of bacteria to antibiotics. Since resistance patterns are so much a reflection of antibiotic usage patterns in an institution, each pediatrician must be aware of the species of bacteria and the resistance patterns of the bacteria isolated in his hospital, particularly in neonatal, intensive care, and burn areas where there is the highest use of antibiotics. Close interaction of pediatrician, diagnostic microbiology laboratory, and hospital epidemiologist can provide early clues to possible bacteria involved in infection, as well as suspected antibiotic resistance patterns.19761253540
532130.9647Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Disruption-deletion cassettes are powerful tools used to study gene function in many organisms, including Saccharomyces cerevisiae. Perhaps the most widely useful of these are the heterologous dominant drug resistance cassettes, which use antibiotic resistance genes from bacteria and fungi as selectable markers. We have created three new dominant drug resistance cassettes by replacing the kanamycin resistance (kan(r)) open reading frame from the kanMX3 and kanMX4 disruption-deletion cassettes (Wach et al., 1994) with open reading frames conferring resistance to the antibiotics hygromycin B (hph), nourseothricin (nat) and bialaphos (pat). The new cassettes, pAG25 (natMX4), pAG29 (patMX4), pAG31 (patMX3), pAG32 (hphMX4), pAG34 (hphMX3) and pAG35 (natMX3), are cloned into pFA6, and so are in all other respects identical to pFA6-kanMX3 and pFA6-kanMX4. Most tools and techniques used with the kanMX plasmids can also be used with the hph, nat and patMX containing plasmids. These new heterologous dominant drug resistance cassettes have unique antibiotic resistance phenotypes and do not affect growth when inserted into the ho locus. These attributes make the cassettes ideally suited for creating S. cerevisiae strains with multiple mutations within a single strain.199910514571
2509140.9646Trends in antimicrobial-drug resistance in Japan. Multidrug resistance in gram-positive bacteria has become common worldwide. In Japan until recently, gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens were controlled by carbapenems, fluoroquinolones, and aminoglycosides. However, several of these microorganisms have recently developed resistance against many antimicrobial drugs.200011076714
5067150.9645Stepwise Evolution of a Klebsiella pneumoniae Clone within a Host Leading to Increased Multidrug Resistance. Five bla(CTX-M-14)-positive Klebsiella pneumoniae isolates (KpWEA1, KpWEA2, KpWEA3, KpWEA4-1, and KpWEA4-2) were consecutively obtained from a patient with relapsed acute myeloid leukemia who was continuously administered antimicrobials. Compared with KpWEA1 and KpWEA2, KpWEA3 showed decreased susceptibility to antimicrobials, and KpWEA4-1 and KpWEA4-2 (isolated from a single specimen) showed further-elevated multidrug-resistance (MDR) phenotypes. This study aims to clarify the clonality of the five isolates and their evolutionary processes leading to MDR by comparison of these complete genomes. The genome comparison revealed KpWEA1 was the antecedent of the other four isolates, and KpWEA4-1 and KpWEA4-2 independently emerged from KpWEA3. Increasing levels of MDR were acquired by gradual accumulation of genetic alterations related to outer membrane protein expression: the loss of OmpK35 and upregulation of AcrAB-TolC occurred in KpWEA3 due to ramA overexpression caused by a mutation in ramR; then OmpK36 was lost in KpWEA4-1 and KpWEA4-2 by different mechanisms. KpWEA4-2 further acquired colistin resistance by the deletion of mgrB. In addition, we found that exuR and kdgR, which encode repressors of hexuronate metabolism-related genes, were disrupted in different ways in KpWEA4-1 and KpWEA4-2. The two isolates also possessed different amino acid substitutions in AtpG, which occurred at very close positions. These genetic alterations related to metabolisms may compensate for the deleterious effects of major porin loss. Thus, our present study reveals the evolutionary process of a K. pneumoniae clone leading to MDR and also suggests specific survival strategies in the bacteria that acquired MDR by the genome evolution. IMPORTANCE Within-host evolution is a survival strategy that can occur in many pathogens and is often associated with the emergence of novel antimicrobial-resistant (AMR) bacteria. To analyze this process, suitable sets of clinical isolates are required. Here, we analyzed five Klebsiella pneumoniae isolates which were consecutively isolated from a patient and showed a gradual increase in the AMR level. By genome sequencing and other analyses, we show that the first isolate was the antecedent of the later isolates and that they gained increased levels of antimicrobial resistance leading to multidrug resistance (MDR) by stepwise changes in the expression of outer membrane proteins. The isolates showing higher levels of MDR lost major porins but still colonized the patient's gut, suggesting that the deleterious effects of porin loss were compensated for by the mutations in hexuronate metabolism-related genes and atpG, which were commonly detected in the MDR isolates.202134817239
1836160.9645Comparative genomics with a multidrug-resistant Klebsiella pneumoniae isolate reveals the panorama of unexplored diversity in Northeast Brazil. The emergence of community acquired infections increases the public health concern on K. pneumoniae and closely related bacteria among which antimicrobial resistance spreads. We report a multidrug-resistant K. pneumoniae isolate, B31, of a patient infected in the community and admitted to an intensive care unit in Northeast Brazil. Antimicrobial susceptibility and genome information were thoroughly investigated to characterize B31 in front of 172 sequenced strains of different countries. Assigned to the Sequence Type 15, which is globally spread, B31 presented extended spectrum beta-lactamase, tigecycline and ciprofloxacin resistance. Genome sequencing revealed most resistance genes being carried by plasmids with high dissemination potential. The absence of main virulence factors, like yersiniabactin and colibactin, apparently suggests a mild pathogenic strain which, on the contrary, persisted and caused severe infection in a previously healthy patient. The present study contributes to unveil the unclear genomic scenario of virulent and multidrug-resistant K. pneumoniae in Brazil.202133373662
2510170.9645Diagnosis of Multidrug-Resistant Pathogens of Pneumonia. Hospital-acquired pneumonia and ventilator-associated pneumonia that are caused by multidrug resistant (MDR) pathogens represent a common and severe problem with increased mortality. Accurate diagnosis is essential to initiate appropriate antimicrobial therapy promptly while simultaneously avoiding antibiotic overuse and subsequent antibiotic resistance. Here, we discuss the main conventional phenotypic diagnostic tests and the advanced molecular tests that are currently available to diagnose the primary MDR pathogens and the resistance genes causing pneumonia.202134943524
228180.9644Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases. Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacteria. Therefore, elucidation of the emerging mechanisms of resistance to nonribosomal peptide antibiotics is critical to their implementation. Here we describe a networking-associated genome-mining platform for linking biosynthetic building blocks to resistance components associated with biosynthetic gene clusters. By applying this approach to 5,585 complete bacterial genomes spanning the entire domain of bacteria, with subsequent chemical and enzymatic analyses, we demonstrate a mechanism of resistance toward nonribosomal peptide antibiotics that is based on hydrolytic cleavage by D-stereospecific peptidases. Our finding reveals both the widespread distribution and broad-spectrum resistance potential of D-stereospecific peptidases, providing a potential early indicator of antibiotic resistance to nonribosomal peptide antibiotics.201829483640
2514190.9644Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae. Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen that can cause a range of infections in hospitalized patients. With the growing use of antibiotics, MDR K. pneumoniae is more prevalent, posing additional difficulties and obstacles in clinical therapy. To provide a valuable reference to deeply understand K. pneumoniae, and also to provide the theoretical basis for clinical prevention of such bacteria infections, the antibiotic resistance and mechanism of K. pneumoniae are discussed in this article. We conducted a literature review on antibiotic resistance of K. pneumoniae. We ran a thorough literature search of PubMed, Web of Science, and Scopus, among other databases. We also thoroughly searched the literature listed in the papers. We searched all antibiotic resistance mechanisms and genes of seven important antibiotics used to treat K. pneumoniae infections. Antibiotics such as β-lactams, aminoglycosides, and quinolones are used in the treatment of K. pneumoniae infection. With both chromosomal and plasmid-encoded ARGs, this pathogen has diverse resistance genes. Carbapenem resistance genes, enlarged-spectrum β-lactamase genes, and AmpC genes are the most often β-lactamase resistance genes. K. pneumoniae is a major contributor to antibiotic resistance worldwide. Understanding K. pneumoniae antibiotic resistance mechanisms and molecular characteristics will be important for the design of targeted prevention and novel control strategies against this pathogen.202337197355