TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Genetic and Functional Analysis of the pks Gene in Clinical Klebsiella pneumoniae Isolates.

The pks gene cluster encodes colibactin, which can cause DNA damage and enhance the virulence in Escherichia coli. However, the role of the pks gene in Klebsiella pneumoniae has not been fully discussed. The aim of this study was to analyze the relationship between the pks gene cluster and virulence factors, as well as to assess antibiotic resistance and biofilm formation capacity in clinical isolates of Klebsiella pneumoniae. Thirty-eight of 95 clinical K. pneumoniae strains were pks positive. pks-positive strains usually infected emergency department patients, and pks-negative strains often infected hospitalized patients. The positive rates of K1 capsular serotype and hypervirulence genes (peg-344, rmpA, rmpA2, iucA, and iroB) were significantly higher in the pks-positive isolates than the pks-negative isolates (P < 0.05). The biofilm formation ability of pks-positive isolates was stronger than that of pks-negative isolates. Antibacterial drug susceptibility test showed the resistance of pks-positive isolates was weaker than that of pks-negative isolates. In conclusion, patients with pks-positive K. pneumoniae infection might have worse treatment outcomes and prognosis. pks-positive K. pneumoniae might have stronger virulence and pathogenicity. Clinical infection with pks-positive K. pneumoniae needs further attention. IMPORTANCE The infection rate with pks-positive K. pneumoniae has been increasing in recent years. Two previous surveys in Taiwan reported 25.6% pks gene islands and 16.7% pks-positive K. pneumoniae strains in bloodstream infections, and Chinese scholars also did a survey of K. pneumoniae bloodstream infections in Changsha, China, and found 26.8% pks-positive K. pneumoniae. In addition, it was found that the pks gene cluster might encode colibactin, which could be related to the virulence of K. pneumoniae. Studies confirmed that the prevalence of colibactin-producing K. pneumoniae was increasing. It is necessary to consider the clear relationship between the pks gene cluster and high pathogenicity in K. pneumoniae.