Phospholipid transporter MlaFEDCB regulates Klebsiella pneumoniae virulence by modulating fimbriae synthesis and stress-adaptive growth.

BACKGROUND Klebsiella pneumoniae is a key opportunistic pathogen, and its emerging hyper-virulent 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 = 0.0005). 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 to the WT-KP strain. The growth of the KP-ΔmlaFEDCB strain was significantly compromised in comparison to the wild-type strain under stress conditions. CONCLUSION 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.