AUTHOR=Wang Lingbo , Zhang Yi , Liu Yan , Xu Mengxin , Yao Zhuocheng , Zhang Xiaodong , Sun Yao , Zhou Tieli , Shen Mo 

TITLE=Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.997310

DOI=10.3389/fmicb.2022.997310

ISSN=1664-302X

ABSTRACT=<p>The rise in infections caused by the hypervirulent carbapenem-resistant <italic>Klebsiella pneumoniae</italic> (hv-CRKP) is an emergent threat to public health. We assessed the effects of chlorogenic acid (CA), a natural phenolic compound, on antibacterial, antivirulence, and anti-quorum sensing (QS) of hv-CRKP. Five hv-CRKP were selected for antimicrobial susceptibility test and confirmed to carry virulence genes and carbapenem-resistant genes by polymerase chain reaction (PCR). Subsequently, a series of time-kill assay, determinations of protease activity and capsule content, biofilm-related experiment, scanning electron microscopy (SEM) and transmission electron microscope (TEM) observation, <italic>G. mellonella</italic> infection model, quantitative real-time PCR (qRT-PCR) of QS-related genes and biofilm formation genes, as well as AI-2 binding test were conduct to verify the effect of CA on hv-CRKP. Five CRKP strains showed varying degrees of resistance to antibacterial agents. All strains carried the <italic>bla</italic><sub><italic>KPC</italic>–2</sub> gene, primarily carrying <italic>rmpA2</italic>, <italic>iucA</italic>, and <italic>peg-344</italic>. CA showed no effect on CRKP growth at the 1/2 minimum inhibitory concentration (MIC), 1/4 MIC, and 1/8 MIC, CA could reduce the production of extracellular protease and capsular polysaccharides, and improve the survival rate of larvae in <italic>Galleria mellonella</italic> (<italic>G. mellonella</italic>) infection model. By means of crystal violet staining and scanning electron microscopy experiments, we observed that CA can inhibit the formation of CRKP biofilm. On the quantitative real-time PCR analysis, the expression of the <italic>luxS</italic>, <italic>mrkA</italic> and <italic>wbbm</italic> genes in most CRKP strains appeared downregulated because of the CA treatment. Besides, CA significantly inhibited the effect of AI-2 activity of BB170. Our study suggests that CA can be an effective antimicrobial, antivirulent compound that can target QS in hv-CRKP infections, thus providing a new therapeutic direction for treating bacterial infections.</p>