Bacterial Chitinases and Their Role in Human Infection

Devlin, Jason R; Behnsen, Judith

doi:10.1128/iai.00549-22

Cited by 4 publications

(6 citation statements)

References 126 publications

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“…ChiC has been described as a virulence factor ( 56 , 57 ), and considering the importance of chitinases in pathogenicity ( 16 – 19 ), we conducted an evaluation of the impact of ChiC in a murine intratracheal (IT) infection model. Female CD1 mice (10 weeks old) were IT-infected with 1.5 × 10 7 CFU/mouse for both the WT PA strain (PAO1) and the chiC ::ISphoA/hah transposon insertion mutant (PW4487).…”

Section: Resultsmentioning

confidence: 99%

Exploring roles of the chitinase ChiC in modulating Pseudomonas aeruginosa virulence phenotypes

Edvardsen,

Askarian,

Zurich

et al. 2024

Microbiol Spectr

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Chitinases are ubiquitous enzymes involved in biomass degradation and chitin turnover in nature. Pseudomonas aeruginosa (PA), an opportunistic human pathogen, expresses ChiC, a secreted glycoside hydrolase 18 family chitinase. Despite speculation about ChiC’s role in PA disease pathogenesis, there is scant evidence supporting this hypothesis. Since PA cannot catabolize chitin, we investigated the potential function(s) of ChiC in PA pathophysiology. Our findings show that ChiC exhibits activity against both insoluble (α- and β-chitin) and soluble chitooligosaccharides. Enzyme kinetics toward (GlcNAc) 4 revealed a k cat of 6.50 s −1 and a K M of 1.38 mM, the latter remarkably high for a canonical chitinase. In our label-free proteomics investigation, ChiC was among the most abundant proteins in the Pel biofilm, suggesting a potential contribution to PA biofilm formation. Using an intratracheal challenge model of PA pneumonia, the chiC ::ISphoA/hah transposon insertion mutant paradoxically showed slightly increased virulence compared to the wild-type parent strain. Our results indicate that ChiC is a genuine chitinase that contributes to a PA pathoadaptive pathway. IMPORTANCE In addition to performing chitin degradation, chitinases from the glycoside hydrolase 18 family have been found to play important roles during pathogenic bacterial infection. Pseudomonas aeruginosa is an opportunistic pathogen capable of causing pneumonia in immunocompromised individuals. Despite not being able to grow on chitin, the bacterium produces a chitinase (ChiC) with hitherto unknown function. This study describes an in-depth characterization of ChiC, focusing on its potential contribution to the bacterium’s disease-causing ability. We demonstrate that ChiC can degrade both polymeric chitin and chitooligosaccharides, and proteomic analysis of Pseudomonas aeruginosa biofilm revealed an abundance of ChiC, hinting at a potential role in biofilm formation. Surprisingly, a mutant strain incapable of ChiC production showed higher virulence than the wild-type strain. While ChiC appears to be a genuine chitinase, further investigation is required to fully elucidate its contribution to Pseudomonas aeruginosa virulence, an important task given the evident health risk posed by this bacterium.

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Section: Resultsmentioning

confidence: 99%

Exploring roles of the chitinase ChiC in modulating Pseudomonas aeruginosa virulence phenotypes

Edvardsen,

Askarian,

Zurich

et al. 2024

Microbiol Spectr

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“…The potential for allergic reactions or immune-mediated diseases raises concerns about their impact on civilian populations. For instance, a recent review by Devlin and Behnsen ( 2023 ) highlighted chitinase’s status as a potent virulence factor in WHO critically ranked bacterial pathogens and further discussed its role during gastrointestinal, respiratory and systemic infections (Fig. 7 ).…”

Section: Biotechnological Exploits Of Chitinasesmentioning

confidence: 99%

“…7 The interaction of bacterial chitinases/chitin binding proteins (CBPs) with molecular targets that are relevant to human and mammalian infection. (Source: Devlin and Behnsen ( 2023 ) copyright © American Society for Microbiology Infect Immun 91(7): e00549-22 …”

Section: Biotechnological Exploits Of Chitinasesmentioning

confidence: 99%

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Chitinases: expanding the boundaries of knowledge beyond routinized chitin degradation.

Unuofin,

Odeniyi,

Majengbasan

et al. 2024

Environ Sci Pollut Res

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Chitinases, enzymes that degrade chitin, have long been studied for their role in various biological processes. They play crucial roles in the moulting process of invertebrates, the digestion of chitinous food, and defense against chitin-bearing pathogens. Additionally, chitinases are involved in physiological functions in crustaceans, such as chitinous food digestion, moulting, and stress response. Moreover, chitinases are universally distributed in organisms from viruses to mammals and have diverse functions including tissue degradation and remodeling, nutrition uptake, pathogen invasion, and immune response regulation. The discovery of these diverse functions expands our understanding of the biological significance and potential applications of chitinases. However, recent research has shown that chitinases possess several other functions beyond just chitin degradation. Their potential as biopesticides, therapeutic agents, and tools for bioremediation underscores their significance in addressing global challenges. More importantly, we noted that they may be applied as bioweapons if ethical regulations regarding production, engineering and application are overlooked.

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“…In addition, the QS system regulates a multitude of virulence factors, comprising chitinase which breaks down chitin for the carbon source ( Devlin and Behnsen, 2023 ) and target immune system components such as mucins and surface glycans, collagenase, cytolytic toxins (hemolysin and leukotoxins) which are detrimental to host cellular functions, exopolysaccharides of bacterial biofilms, flagellar proteins, lipases, metalloproteases, swarming motility, exoprotease synthesis, T2SS and T3SS ( Miller et al, 1988 ; de Oca-Mejía et al, 2015 ). C. violaceum does indeed have type IV pili machinery, which is crucial for twitching mobility, bacterial aggregation and also host adhesion in addition to a single flagellum and as an outcome, escalating pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

Regulation of virulence in Chromobacterium violaceum and strategies to combat it

Venkatramanan,

Nalini

2024

Front. Microbiol.

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Chromobacterium is a rod-shaped, Gram-negative, facultatively anaerobic bacteria with a cosmopolitan distribution. Just about 160 Chromobacterium violaceum incidents have been reported globally, but then once infected, it has the ability to cause deadly septicemia, and infections in the lungs, liver, brain, spleen, and lymphatic systems that might lead to death. C. violaceum produces and utilizes violacein to kill bacteria that compete with it in an ecological niche. Violacein is a hydrophobic bisindole that is delivered through an efficient transport route termed outer membrane vesicles (OMVs) through the aqueous environment. OMVs are small, spherical segments detached from the outer membrane of Gram-negative bacteria. C. violaceum OMV secretions are controlled by a mechanism called the quorum sensing system CviI/CviR, which enables cell-to-cell communication between them and regulation of various virulence factors such as biofilm formation, and violacein biosynthesis. Another virulence factor bacterial type 3 secretion system (T3SS) is divided into two types: Cpi-1 and Cpi-2. Cpi-1’s needle and rod effector proteins are perhaps recognized by NAIP receptors in humans and mice, activating the NLRC4 inflammasome cascade, effectively clearing spleen infections via pyroptosis, and cytotoxicity mediated by IL-18-driven Natural killer (NK) cells in the liver. In this paper, we attempt to interrelate quorum-controlled biofilm formation, violacein production, violacein delivery by OMVs and T3SS effector protein production and host mediated immunological effects against the Cpi1 of T3SS. We suggest a research path with natural bioactive molecule like palmitic acid that can act as an anti-quorum agent by reducing the expression of virulence factors as well as an immunomodulatory agent that can augment innate immune defense by hyperactivation of NLRC4 inflammasome hence dramatically purge C. violaceum infections.

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Bacterial Chitinases and Their Role in Human Infection

Cited by 4 publications

References 126 publications

Exploring roles of the chitinase ChiC in modulating Pseudomonas aeruginosa virulence phenotypes

Exploring roles of the chitinase ChiC in modulating Pseudomonas aeruginosa virulence phenotypes

Chitinases: expanding the boundaries of knowledge beyond routinized chitin degradation.

Regulation of virulence in Chromobacterium violaceum and strategies to combat it

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