Affiliation:
1. Department of Bacteriology, Capital Institute of Pediatrics , Beijing, China
2. Graduate School of Peking Union Medical College , Beijing, China
3. University of Edinburgh , Edinburgh, United Kingdom
Abstract
ABSTRACT
Klebsiella pneumoniae
is a well-known human nosocomial pathogen with an arsenal of virulence factors, including capsular polysaccharides (CPS), fimbriae, flagella, and lipopolysaccharides (LPS). Our previous study found that alcohol acted as an essential virulence factor for high-alcohol-producing
K. pneumoniae
(HiAlc
Kpn
). Integration host factor (IHF) is a nucleoid-associated protein that functions as a global virulence regulator in
Escherichia coli
. However, the regulatory role of IHF in
K. pneumoniae
remains unknown. In the present study, we found that deletion of
ihfA
or
ihfB
resulted in a slight defect in bacterial growth, a severe absence of biofilm formation and cytotoxicity, and a significant reduction in alcohol production. RNA sequencing differential gene expression analysis showed that compared with the wild-type control, the expression of many virulence factor genes was downregulated in Δ
ihfA
and Δ
ihfB
strains, such as those related to CPS (
rcsA
,
galF
,
wzi
, and
iscR
), LPS (
rfbABCD
), type I and type III fimbriae (
fim
and
mrk
operon), cellulose (
bcs
operon), iron transporter (
feoABC
,
fhuA
,
fhuF
,
tonB
,
exbB
, and
exbD
), quorum sensing (
lsr
operon and
sdiA
), type II secretion system (T2SS) and type VI secretion system (T6SS) (
tssG
,
hcp
, and
gspE
). Of these virulence factors, CPS, LPS, fimbriae, and cellulose are involved in biofilm formation. In addition, IHF could affect the alcohol production by regulating genes related to glucose intake (
ptsG
), pyruvate formate-lyase, alcohol dehydrogenase, and the tricarboxylic acid (TCA) cycle. Our data provided new insights into the importance of IHF in regulating the virulence of HiAlc
Kpn
.
IMPORTANCE
Klebsiella pneumoniae
is a well-known human nosocomial pathogen that causes various infectious diseases, including urinary tract infections, hospital-acquired pneumonia, bacteremia, and liver abscesses. Our previous studies demonstrated that HiAlc
Kpn
mediated the development of nonalcoholic fatty liver disease by producing excess endogenous alcohol
in vivo
. However, the regulators regulating the expression of genes related to metabolism, biofilm formation, and virulence of HiAlc
Kpn
remain unclear. In this study, the regulator IHF was found to positively regulate biofilm formation and many virulence factors including CPS, LPS, type I and type III fimbriae, cellulose, iron transporter, AI-2 quorum sensing, T2SS, and T6SS in HiAlc
Kpn
. Furthermore, IHF positively regulated alcohol production in HiAlc
Kpn
. Our results suggested that IHF could be a potential drug target for treating various infectious diseases caused by
K. pneumoniae
. Hence, the regulation of different virulence factors by IHF in
K. pneumoniae
requires further investigation.
Funder
MOST | National Natural Science Foundation of China
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology