Effect of O antigen ligase gene mutation on oxidative stress resistance and pathogenicity of NMEC strain RS218

Wang, Huan; Huang, Li‐Min; Zhang, Tongchao; Zong, Bingbing; Ren, Xuanxiu; Zhu, Yongwei; Song, Fangyu; Wang, Xiangru; Chen, Huanchun; Tan, Chen

doi:10.1016/j.micpath.2019.103656

Cited by 6 publications

(7 citation statements)

References 54 publications

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“…O-antigen, which is one constituent of LPS, is distal to the OM (Raetz and Whitfield, 2002). Previous studies have revealed that O-antigen plays a crucial role in stress tolerance and immune evasion in Gramnegative bacteria (Murray et al, 2006;Berry et al, 2009;Duerr et al, 2009;Wells et al, 2014;Noh et al, 2015;Zheng et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…In Salmonella enterica serovar Typhimurium, the O-antigen helps cells to evade the complement cascade (Murray et al, 2006). In Erwinia amylovora, Bradyrhizobium japonicum, and Escherichia coli, the O-antigen protects cells against oxidative stress (Berry et al, 2009;Noh et al, 2015;Zheng et al, 2019). O-antigen was reported to protect B. japonicum and S. enterica serovar Typhi against osmotic stress (Bittner et al, 2002;Noh et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies showed that the Cpx TCS is related to mediation of host environmental fitness (Ruiz and Silhavy, 2005;Yamamoto and Ishihama, 2006;Vogt and Raivio, 2012;Delhaye et al, 2016;Pezza et al, 2016), that the O-antigen helps bacteria to survive in harsh environments (Bittner et al, 2002;Noh et al, 2015;Silva-Valenzuela et al, 2016;Zheng et al, 2019), and that the CpxAR TCS is activated by overexpression of O-antigen (Bengoechea et al, 2002). However, it remained unclear whether the CpxAR system regulates O-antigen biosynthesis and affects stress resistance in A. pleuropneumoniae.…”

Section: Introductionmentioning

confidence: 99%

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The CpxAR Two-Component System Contributes to Growth, Stress Resistance, and Virulence of Actinobacillus pleuropneumoniae by Upregulating wecA Transcription

et al. 2020

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Actinobacillus pleuropneumoniae is the pathogen of porcine contagious pleuropneumonia. In A. pleuropneumoniae, the CpxAR two-component system is essential for fitness and growth. The O-antigen protrudes from the outer membrane to the exterior of the cell, and the outer membrane serves as a barrier that helps the bacteria to survive in harsh environments. WecA, a undecaprenyl phosphate GlcNAc-1-phosphate transferase, is involved in O-antigen repeating unit biosynthesis. In this study, we investigated the role of CpxAR in the expression of wecA in A. pleuropneumoniae. Our results revealed that CpxR positively regulates wecA expression by directly binding to the putative promoter region of wecA. Wild-type, cpxAR, wecA, and complemented strains were investigated under serum, oxidative, and osmotic stresses. The cpxAR and wecA strains were more susceptible to these stresses than the wild-type, but the complemented strains showed phenotypes similar to those of the wild-type. Mice infected with the cpxAR and wecA strains exhibited lower mortality and bacterial loads in the lung than those infected with the wild-type or complemented strains. This study reveals that the CpxAR two-component system contributes to A. pleuropneumoniae growth, stress resistance, and virulence, by upregulating expression of wecA. Our findings provide new insight into the pathogenesis of A. pleuropneumoniae.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The CpxAR Two-Component System Contributes to Growth, Stress Resistance, and Virulence of Actinobacillus pleuropneumoniae by Upregulating wecA Transcription

et al. 2020

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“…The pUTmini-Tn5 Cm plasmid was transformed into RS218 through conjugation transfer with the donor strain E. coli X7213. The transformants were screened on plates containing chloramphenicol at 50 µg/mL to select the positive insertions, as we previously reported [ 25 ]. Next, the mutants in this library were subjected to the firefly luciferase activity screening, specifically targeting gli2 promotor activity.…”

Section: Methodsmentioning

confidence: 99%

Meningitic Escherichia coli α-hemolysin aggravates blood–brain barrier disruption via targeting TGFβ1-triggered hedgehog signaling

Huo

et al. 2021

Mol Brain

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Bacterial meningitis is a life-threatening infectious disease with severe neurological sequelae and a high mortality rate, in which Escherichia coli is one of the primary Gram-negative etiological bacteria. Meningitic E. coli infection is often accompanied by an elevated blood–brain barrier (BBB) permeability. BBB is the structural and functional barrier composed of brain microvascular endothelial cells (BMECs), astrocytes, and pericytes, and we have previously shown that astrocytes-derived TGFβ1 physiologically maintained the BBB permeability by triggering a non-canonical hedgehog signaling in brain microvascular endothelial cells (BMECs). Here, we subsequently demonstrated that meningitic E. coli infection could subvert this intercellular communication within BBB by attenuating TGFBRII/Gli2-mediated such signaling. By high-throughput screening, we identified E. coli α-hemolysin as the critical determinant responsible for this attenuation through Sp1-dependent TGFBRII reduction and triggering Ca2+ influx and protein kinase A activation, thus leading to Gli2 suppression. Additionally, the exogenous hedgehog agonist SAG exhibited promising protection against the infection-caused BBB dysfunction. Our work revealed a hedgehog-targeted pathogenic mechanism during meningitic E. coli-caused BBB disruption and suggested that activating hedgehog signaling within BBB could be a potential protective strategy for future therapy of bacterial meningitis.

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“…The barrier has been visualized by EM and extends 31-36 nm from the outer membrane surface in P. aeruginosa (134) and 35-70 nm in S. flexneri (135), depending on O-PS structure. Whereas O-PS functions vary with species and (in some cases) specific O-PS chemistry, they often contribute to protection against environmental threats including lysozyme (136), colicins (137), oxidative stress (138), and bile (139). They can also promote resistance to antimicrobial peptides (140)(141)(142), polymyxin (139), and colistin (143), which is predominantly driven by lipid A modifications (3).…”

Section: Impact Of Chain-length Distribution On O-ps Functionmentioning

confidence: 99%

Lipopolysaccharide O-antigens—bacterial glycans made to measure

Whitfield

Williams

Kelly

2020

Journal of Biological Chemistry

116

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Lipopolysaccharides are critical components of bacterial outer membranes. The more conserved lipid A part of the lipopolysaccharide molecule is a major element in the permeability barrier imposed by the outer membrane and offers a pathogen-associated molecular pattern recognized by innate immune systems. In contrast, the long-chain O-antigen polysaccharide (O-PS) shows remarkable structural diversity and fulfills a range of functions depending on bacterial lifestyles. O-PS production is vital for the success of clinically important Gram-negative pathogens. The biological properties and functions of O-PSs are mostly independent of specific structures, but the size distribution of O-PS chains is particularly important in many contexts. Despite the vast O-PS chemical diversity, most are produced in bacterial cells by two assembly strategies and the different mechanisms employed in these pathways to regulate chain-length distribution are emerging. Here, we review our current understanding of the mechanisms involved in regulating O-PS chain-length distribution and discuss their impact on microbial cell biology.

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Effect of O antigen ligase gene mutation on oxidative stress resistance and pathogenicity of NMEC strain RS218

Cited by 6 publications

References 54 publications

The CpxAR Two-Component System Contributes to Growth, Stress Resistance, and Virulence of Actinobacillus pleuropneumoniae by Upregulating wecA Transcription

The CpxAR Two-Component System Contributes to Growth, Stress Resistance, and Virulence of Actinobacillus pleuropneumoniae by Upregulating wecA Transcription

Meningitic Escherichia coli α-hemolysin aggravates blood–brain barrier disruption via targeting TGFβ1-triggered hedgehog signaling

Lipopolysaccharide O-antigens—bacterial glycans made to measure

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