Klebsiella pneumoniae Peptidoglycan-Associated Lipoprotein and Murein Lipoprotein Contribute to Serum Resistance, Antiphagocytosis, and Proinflammatory Cytokine Stimulation

Hsieh, Pei-Fang; Liu, J.-Y.; Pan, Yuwen; Wu, Mao S.; Lin, Tzu‐Lung; Huang, Yu-Tsung; Wang, J.-T.

doi:10.1093/infdis/jit384

Cited by 59 publications

(56 citation statements)

References 27 publications

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“…28 Additionally, some OM proteins contribute significantly to the virulence of K. pneumoniae, by conferring protection against host's innate immunity. 29,30 In this study, we demonstrate that YfgL is the major facilitator of K. pneumoniae adherence. Moreover, the YfgL lipoprotein altered integrity of the OM that affects transcriptional expression of the fim operon and production of type-1 fimbriae in K. pneumoniae.…”

Section: Introductionmentioning

confidence: 55%

“…39,40 Our previous data also demonstrated that capsular polysaccharide (CPS) and OM proteins Pal and LppA, but not OmpA, all play important roles in a PLA K. pneumoniae strain resistance to phagocytosis. 30,41 We showed here that the K. pneumoniae YfgL confers protection against neutrophil phagocytosis, implying that reduced biogenesis of OmpK35/OmpK36 might account for loss of in vivo virulence in the yfgL mutant.…”

Section: Discussionmentioning

confidence: 79%

“…Bacterial strains, plasmids, and primers used in this study are listed in Table S1. 30,31,41,43,51 Gene deletion and complementation. K. pneumoniae mutated in yfgL, clpS, entS, fim, yraM, or pts were constructed using the previously described unmarked deletion method.…”

Section: Methodsmentioning

confidence: 99%

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TheKlebsiella pneumoniaeYfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, andin vivovirulence

et al. 2016

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Klebsiella pneumoniae is an opportunistic pathogen that causes several kinds of infections, including pneumonia, bacteremia, urinary tract infection and community-acquired pyogenic liver abscess (PLA). Adhesion is the critical first step in the infection process. Our previous work demonstrated that the transcellular translocation is exploited by K. pneumoniae strains to migrate from the gut flora into other tissues, resulting in systemic infections. However, the initial stages of K. pneumoniae infection remain unclear. In this study, we demonstrated that a K. pneumoniae strain deleted for yfgL (bamB) exhibited reduced adherence to and invasion of host cells; changed biogenesis of major b-barrel outer membrane proteins; decreased transcriptional expression of type-1 fimbriae; and increased susceptibility to vancomycin and erythromycin. The yfgL deletion mutant also had reduced ability to against neutrophil phagocytosis; exhibited decreased induction of host IL-6 production; and was profoundly attenuated for virulence in a K. pneumoniae model of bacteremia. Thus, the K. pneumoniae YfgL lipoprotein mediates in outer membrane proteins biogenesis and is crucial for anti-phagocytosis and survival in vivo. These data provide a new insight for K. pneumoniae attachment and such knowledge could facilitate preventive therapies or alternative therapies against K. pneumoniae.

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Section: Introductionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 79%

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TheKlebsiella pneumoniaeYfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, andin vivovirulence

et al. 2016

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“…Bacterial lipoproteins are established bacterial virulence factors [11–13,24,26,36] that function as inflammatory stimulants in infection and disease progression. Our study is the first to show pro-inflammatory effects of AaPAL, an outer membrane lipoprotein of a major periodontal pathogen, A. actinomycetemcomitans .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a Hemophilus ducrey PAL-deficient mutant strain was less virulent than its parental strain in a human infection model [23], and B. abortus PAL is one of the lipoproteins which causes production of pro-inflammatory cytokines in brucellosis [12]. Klebsiella pneumoniae PAL protects bacterial cells from serum killing, as well as phagocytosis, and is an important virulence factor in a mouse infection model [24]. In addition, strongly immunogenic PAL of Burkholderia cenocepacia [25] facilitates attachment of this opportunistic pathogen to the lung epithelial cells and stimulates IL-8 secretion in cystic fibrosis [26].…”

Section: Introductionmentioning

confidence: 99%

Peptidoglycan-associated lipoprotein ofAggregatibacter actinomycetemcomitansinduces apoptosis and production of proinflammatory cytokines via TLR2 in murine macrophages RAW 264.7in vitro

Ihalin

Eneslätt

Asikainen

2018

Journal of Oral Microbiology

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Peptidoglycan-associated lipoprotein (PAL) is a conserved pro-inflammatory outer membrane lipoprotein in Gram-negative bacteria. Compared to systemic pathogens, little is known about the virulence properties of PAL in Aggregatibacter actinomycetemcomitans (AaPAL). The aims of this study were to investigate the cytolethality of AaPAL and its ability to induce pro-inflammatory cytokine production in macrophages. Mouse macrophages were stimulated with AaPAL, and the production of IL-1β, IL-6, TNF-α, and MCP-1 was measured after 6, 24, and 48 h. To investigate which receptor AaPAL employs for its interaction with macrophages, anti-toll-like receptor (TLR)2 and anti-TLR4 antibodies were used to block respective TLRs on macrophages. Metabolic activity and apoptosis of the macrophages were investigated after stimulation with AaPAL. AaPAL induced the production of MCP-1, TNF-α, IL-6, and IL-1β from mouse macrophages in order of decreasing abundance. The pre-treatment of macrophages with an anti-TLR2 antibody significantly diminished cytokine production. Under AaPAL stimulation, the metabolic activity of macrophages decreased in a dose- and time-dependent manner. Furthermore, AaPAL induced apoptosis in 56% of macrophages after 48 h of incubation. Our data suggest that AaPAL can kill macrophages by apoptosis. The results also emphasize the role of AaPAL as a potent pro-inflammatory agent in A. actinomycetemcomitans-associated infections.

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Pal Affects the Proliferation in Macrophages and Virulence of Brucella, and as Mucosal Adjuvants, Provides an Effective Protection to Mice Against Salmonella Enteritidis

Chen

Fu²,

Kong

et al. 2022

Curr Microbiol

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The purpose of this study was to elucidate the roles of peptidoglycan-associated lipoprotein (Pal protein) in the proliferation of Brucella in macrophage and bacterial virulence, and to evaluate the immune effect of Pal protein to Salmonella enteritidis . Murine macrophage-like cell line Raw264.7 was stimulated by recombinant Pal protein, and the expression of TNF-α and IFN-γ were up-regulated, but not it of IL-1β and IL-6. The macrophages infection and in vitro simulated stress assays showed that deletion of pal gene reduced the proliferation of Brucella in macrophages, the survival in acidic, oxidative and polymyxin B-contained environment. The mice infection assay showed that mice challenged with the pal mutant strain were found to have more severe splenomegaly, but less bacterial load. After oral immunization of mice, Pal protein induced a higher titer of mucosal and humoral antibody (IgA and IgG) against heat-killed Salmonella enteritidis , and a stronger Th1 cellular immune response. The challengte experiments showed Pal protein elevated the survival rate and reduced the bacterial load of spleens in immunized mice. In conclusion, our results revealed the important roles of pal gene in Brucella virulence, and Pal protein was a potentially valuable adjuvant against mucosal pathogens, such as Salmonella enteritidis . Supplementary Information The online version contains supplementary material available at 10.1007/s00284-022-03107-w.

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Klebsiella pneumoniae Peptidoglycan-Associated Lipoprotein and Murein Lipoprotein Contribute to Serum Resistance, Antiphagocytosis, and Proinflammatory Cytokine Stimulation

Abstract: Our findings indicate that K. pneumoniae Pal and LppA proteins are important in the maintenance of cell integrity, contribute to virulence, and could be used as attenuated vaccines.

Cited by 59 publications

References 27 publications

TheKlebsiella pneumoniaeYfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, andin vivovirulence

TheKlebsiella pneumoniaeYfgL (BamB) lipoprotein contributes to outer membrane protein biogenesis, type-1 fimbriae expression, anti-phagocytosis, andin vivovirulence

Peptidoglycan-associated lipoprotein ofAggregatibacter actinomycetemcomitansinduces apoptosis and production of proinflammatory cytokines via TLR2 in murine macrophages RAW 264.7in vitro

Pal Affects the Proliferation in Macrophages and Virulence of Brucella, and as Mucosal Adjuvants, Provides an Effective Protection to Mice Against Salmonella Enteritidis

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