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Published on: February 23, 2014
Phospholipid Transporter MlaFEDCB Regulates Klebsiella pneumoniae Virulence by Modulating Fimbriae Synthesis and
Xiaoyu Zhao1,2, Haoqi Liu1,2, Qinglan Guo1,2
1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Background:
Klebsiella pneumoniae is a key opportunistic pathogen, and its emerging hypervirulent strains pose a growing public health threat. An association exists between the phospholipid transporter MlaFEDCB and bacterial virulence; however, its regulatory role and underlying mechanisms remain elusive. Herein, we focused on K. pneumoniae virulence regulation via mlaFEDCB under in vitro and in vivo conditions.
Methods And Results:
Homology analysis showed that mlaFEDCB gene cluster is highly conservative among gram-negative bacterial strains and is contiguously arranged and co-transcribed within the genome. Experiment involving murine intraperitoneal infection revealed that mice infected with KP-ΔmlaFEDCB strain showed substantially prolonged survival (P = .0005). Furthermore, transcriptomic analysis showed altered expression of virulence-associated genes, especially fimH and fimD, which are involved in fimbrial structure and host cell adherence. Scanning electron and transmission electron microscopy showed that the WT-KP strain demonstrated a complex fibrous fimbrial network, with several long, thin structures interwoven with those of neighboring bacteria, whereas the KP-ΔmlaFEDCB strain showed markedly fewer fimbriae and lacked the fimbrial network. Furthermore, bladder epithelial cells adhesion assay showed an apparent reduction in the KP-ΔmlaFEDCB strain compared with the WT-KP strain. The growth of the KP-ΔmlaFEDCB strain was significantly compromised in comparison to the wild-type strain under stress conditions.
Conclusions:
Thus, mlaFEDCB gene cluster increases the adhesion, invasion, and environmental adaptability of K. pneumoniae by modulating virulence-related gene expression, pilus synthesis, and growth under stress conditions.
Insights
The mlaFEDCB gene cluster in Klebsiella pneumoniae enhances bacterial virulence by increasing adhesion and adaptability. Deleting this cluster significantly improves survival in mice and reduces bacterial fimbriae and adherence.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Klebsiella pneumoniae is a significant opportunistic pathogen with emerging hyper-virulent strains.
- The phospholipid transporter MlaFEDCB is linked to bacterial virulence, but its regulatory mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of the mlaFEDCB gene cluster in regulating Klebsiella pneumoniae virulence.
- To elucidate the mechanisms by which mlaFEDCB influences bacterial adaptation and host interaction.
Main Methods:
- Homology analysis of the mlaFEDCB gene cluster.
- Murine intraperitoneal infection models.
- Transcriptomic analysis to assess gene expression.
- Electron microscopy (SEM, TEM) to visualize fimbrial structures.
- Adhesion assays with bladder epithelial cells.
- Growth assays under stress conditions.
Main Results:
- The mlaFEDCB gene cluster is conserved and co-transcribed in gram-negative bacteria.
- Deletion of mlaFEDCB (KP-ΔmlaFEDCB) significantly increased mouse survival and reduced fimbrial structures and host cell adhesion.
- Transcriptomic analysis revealed altered expression of virulence genes, including fimH and fimD, in the mutant strain.
- KP-ΔmlaFEDCB exhibited compromised growth under stress conditions compared to wild-type K. pneumoniae.
Conclusions:
- The mlaFEDCB gene cluster is crucial for Klebsiella pneumoniae virulence.
- mlaFEDCB modulates virulence gene expression, pilus synthesis, and environmental adaptability.
- Targeting mlaFEDCB could be a strategy to combat K. pneumoniae infections.
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