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Control of infections caused by carbapenem-resistant continues to be challenging. The success of this pathogen is favored by its ability to acquire antimicrobial resistance and to spread and persist in both the environment and in humans. The emergence of clinically important clones, such as sequence types 11, 15, 101, and 258, has been reported worldwide. However, the mechanisms promoting the dissemination of such high-risk clones are unknown. Unraveling the factors that play a role in the pathobiology and epidemicity of is therefore important for managing infections. To address this issue, we studied a carbapenem-resistant ST-15 isolate (Kp3380) that displayed a remarkable adherent phenotype with abundant pilus-like structures. Genome sequencing enabled us to identify a chaperone-usher pili system (Kpi) in Kp3380. Analysis of a large population from 32 European countries showed that the Kpi system is associated with the ST-15 clone. Phylogenetic analysis of the operon revealed that Kpi belongs to the little-characterized γ-fimbrial clade. We demonstrate that Kpi contributes positively to the ability of to form biofilms and adhere to different host tissues. Moreover, the in vivo intestinal colonizing capacity of the Kpi-defective mutant was significantly reduced, as was its ability to infect The findings provide information about the pathobiology and epidemicity of Kpi and indicate that the presence of Kpi may explain the success of the ST-15 clone. Disrupting bacterial adherence to the intestinal surface could potentially target gastrointestinal colonization.
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http://dx.doi.org/10.1073/pnas.1921393117 | DOI Listing |
bioRxiv
August 2025
Department of Biochemistry, University of Washington, Seattle, WA, USA.
The rise of multidrug-resistant bacterial infections necessitates the discovery of novel antimicrobial strategies. Here, we show that protein design provides a generalizable means of generating new antimicrobials by neutralizing the function of bacterial adhesins, which are virulence factors critical in host-pathogen interactions. We designed high-affinity miniprotein binders to FimH and Abp1D/Abp2D chaperone usher pili adhesins from uropathogenic and , respectively, which are implicated in mediating both uncomplicated and catheter-associated urinary tract infections (UTI) responsible for significant morbidity and mortality worldwide.
View Article and Find Full Text PDFBiofilm
June 2025
Department of Biology, Purdue School of Science, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA.
is an emerging multidrug-resistant, Gram-negative opportunistic pathogen. It causes many healthcare-associated infections such as sepsis, endocarditis, meningitis, and catheter-related urinary tract infections. It also affects individuals with cystic fibrosis, exacerbating their lung condition.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2025
The Second Clinical Medical College, Guangzhou University of Chinese Medicine, State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
is a major opportunistic pathogen that causes chronic infections, particularly in patients with cystic fibrosis and chronic obstructive pulmonary disease (COPD). The type VI secretion system (T6SS) is a primary virulence factor of in chronic infections. The objective of this study was to elucidate the regulatory mechanisms and pathogenic effects of the T6SS during infection, utilizing transcriptome sequencing and functional assays.
View Article and Find Full Text PDFPLoS Genet
May 2025
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America.
Burkholderia thailandensis strain E264 (BtE264) and close relatives stochastically duplicate a 208.6 kb region of chromosome I via RecA-dependent recombination between two nearly identical insertion sequence elements. Because homologous recombination occurs at a constant, low level, populations of BtE264 are always heterogeneous, but cells containing two or more copies of the region (Dup+) have an advantage, and hence predominate, during biofilm growth, while those with a single copy (Dup-) are favored during planktonic growth.
View Article and Find Full Text PDFStructure
June 2025
Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan; Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Researc
Pathogenic bacteria utilize a variety of pilus filaments to colonize intestinal epithelia, including those synthesized by the chaperone-usher or type IV pilus assembly pathway. Despite the importance of these filaments as potential drug and vaccine targets, their large size and dynamic nature make high-resolution structure determination challenging. Here, we used cryo-electron microscopy (cryo-EM) and whole-genome sequencing to determine the structures of type I and IV pili expressed in enterotoxigenic Escherichia coli.
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