Cell wall thickness and the molecular mechanism of heterogeneous vancomycin‐intermediate<i>Staphylococcus aureus</i>

Cui, Jiewei; Zhang, Hongxu; Mo, Zhenfei; Yu, Mingzi; Liang, Zhixin

doi:10.1111/lam.13456

Cited by 17 publications

(12 citation statements)

References 24 publications

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“…This may be due to their similarity in tolerance to low level vancomycin (both the hVISA and the VISA had higher PAP-AUC values than those of the VSSA) [12]. In addition, our previous study and a recent report showed that the hVISA isolates also had thickening cell wall, though not as thick as that of the VISA isolates [20,21]. The vancomycin MIC of the VISA isolates in this study was slightly higher than those of the hVISA and the VSSA isolates.…”

Section: Discussionmentioning

confidence: 77%

“…Though the target site of vancomycin is D-alanyl-D-alanine residue of the cell wall [23], it may have indirect effect to other intracellular components of the bacterial cells such as cell membrane, ribosome, and DNA [23]. The VISA and the hVISA cells had thickening cell wall and increasing free D-alanyl-Dalanine residues, leading to vancomycin blockage from reaching its target site [21,24]. This may be the reason of lower stress response of the VISA and the hVISA to vancomycin than that of the VSSA.…”

Section: Discussionmentioning

confidence: 99%

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Preliminary study on small angle X-ray scattering patterns of intact vancomycin susceptible and non-susceptible Staphylococcus aureus cells

Wongthong¹,

Kamonsutthipaijit²,

Kaewhan³

et al. 2022

ScienceAsia

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Low-level vancomycin-resistant S. aureus designated as heterogeneous vancomycin-intermediate S. aureus (hVISA) have been associated with treatment failure and unable to detect by routine disk diffusion method. As small angle X-ray scattering (SAXS) can be used for studying size, shape, and biology structure of bacterial cells; thus, this study aimed to investigate the SAXS patterns of biomolecules of vancomycin susceptible S. aureus (VSSA), hVISA, and, VISA cells. A total of 9 S. aureus isolates, 3 each from VSSA, hVISA, and VISA groups, were cultured on brain heart infusion agar with and without vancomycin. The cultured cells were kept overnight to reach their exponential phase and subjected to the SAXS using beamline 1.3W: SAXS. Under vancomycin untreated condition, the VISA cells showed different SAXS pattern from those of the VSSA and the hVISA, whereas the vancomycin treated cells of hVISA and VISA displayed similar SAXS patterns. The ribosome of VSSA was significantly smaller than that of hVISA under the untreated condition but showed no statistically different under the treated condition. In addition, when compared the ribosome and the DNA of VSSA with the VISA's and the DNA of VISA with the hVISA's, they were different only under the untreated condition. This preliminary study showed that under the stress condition mediated by vancomycin, the vancomycin non-susceptible S. aureus (hVISA and VISA) had similar SAXS patterns; while under the non-stress condition, the VSSA and hVISA showed similar patterns. This study provides preliminary information on bacterial adaptation under vancomycin-mediated stress condition.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Preliminary study on small angle X-ray scattering patterns of intact vancomycin susceptible and non-susceptible Staphylococcus aureus cells

Wongthong¹,

Kamonsutthipaijit²,

Kaewhan³

et al. 2022

ScienceAsia

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“…Then, shotgun proteomics LC-MS/MS analysis identified all of the pulled-down proteins, and we found 18 differential proteins ( Figure 1 ). GO functional analysis revealed that GlmS, a metabolite interconversion enzyme, has catalytic activity and participates in cellular processes and metabolic processes [ 10 , 32–34 ]. KEGG pathway analysis indicated that GlmS may be related to the N-acetylglucosamine metabolism pathway, which can affect the cell wall synthesis of S. aureus [ 10 , 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…This discovery is very unexpected and interesting. To date, research on glmS has mainly focused on cell wall synthesis, drug resistance, and the development of antibiotic targets [ 11 , 32 , 34 ], but no research has shown its roles in the global regulation and pathogenicity of S. aureus thus far. In previous studies, riboswitches have been classified as a family of 5’-untranslated mRNA regions mostly found in bacteria.…”

Section: Discussionmentioning

confidence: 99%

GlmS plays a key role in the virulence factor expression and biofilm formation ability of Staphylococcus aureus promoted by advanced glycation end products

Ni,

Shen,

Luo

et al. 2024

Virulence

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Staphylococcus aureus (S. aureus) is well known for its biofilm formation ability and is responsible for serious, chronic refractory infections worldwide. We previously demonstrated that advanced glycation end products (AGEs), a hallmark of chronic hyperglycaemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via sigB upregulation in S. aureus , contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used pull-down assay and LC-MS/MS to identify the GlmS as a candidate regulator of sigB in S. aureus stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of sigB . We constructed NCTC 8325 ∆ glmS for further validation. qRT-PCR analysis revealed that AGEs promoted both glmS and sigB expression in the NCTC 8325 strain but had no effect on NCTC 8325 ∆ glmS . NCTC 8325 ∆ glmS showed a significant attenuation in biofilm formation and virulence factor expression, accompanied by a decrease in sigB expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased haemolysis ability, downregulation of hla and hld expression, and less and sparser biofilms, indicated that sigB and biofilm formation ability no longer responded to AGEs in NCTC 8325 ∆ glmS . Our data extend the understanding of GlmS in the global regulatory network of S. aureus and demonstrate a new mechanism by which AGEs can upregulate GlmS, which directly regulates sigB and plays a significant role in mediating biofilm formation and virulence factor expression.

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“…Cell wall thickness is influenced by autolysis, peptidoglycan crosslinking and cell wall synthesis (42,43). In S. aureus, cell wall synthesis can increase upon cell wall stress induced by antibiotics.…”

Section: Discussionmentioning

confidence: 99%

C-di-AMP levels modulateStaphylococcus aureuscell wall thickness as well as virulence and contribute to antibiotic resistance and tolerance

Haunreiter

Tarnutzer

Bär

et al. 2023

Preprint

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Beta-lactam antibiotics are widely used to treat infections caused by the important human pathogen Staphylococcus aureus. Resistance to beta-lactams, as found in methicillin-resistant S. aureus (MRSA), renders effective treatment difficult. The second messenger cyclic di-3′,5′-adenosine monophosphate (c-di-AMP) promotes beta-lactam resistance in clinical S. aureus isolates. C-di-AMP plays a crucial role in the regulation of cellular processes such as virulence, cell wall homeostasis and resistance to beta-lactams in many bacterial species. In S. aureus, c-di-AMP synthesis is mediated by the diadenylate cyclase DacA, while its degradation is carried out by the phosphodiesterases GdpP and Pde2. In this work, we assessed the effect of altered c-di-AMP levels due to mutations in cacA, gdpP or gdpP/pde2 on virulence determinants. We report that a previously described growth defect in bacteria producing high c-di-AMP levels is mainly attributable to smaller cell size. High c-di-AMP levels also led to decreased survival upon oxidative stress, reduced production of the antioxidant staphyloxanthin, increased oxacillin and fosfomycin resistance and increased cell wall thickness. While resistance to ceftaroline was not affected, high c-di-AMP levels promoted tolerance to this antibiotic. In response to cell wall stress induced by antibiotics, the three-component regulatory system VraTSR mediates an increase in cell wall synthesis via the cell wall stress stimulon (CWSS). Increased c-di-AMP levels led to an activation of the CWSS. Upon deletion of vraR, resistance to oxacillin and fosfomycin as well as cell wall thickness diminished in the ΔgdpP mutant, indicating a contribution of the VraTSR system to the cell wall related phenotypes.

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Cell wall thickness and the molecular mechanism of heterogeneous vancomycin‐intermediateStaphylococcus aureus

Cited by 17 publications

References 24 publications

Preliminary study on small angle X-ray scattering patterns of intact vancomycin susceptible and non-susceptible Staphylococcus aureus cells

Preliminary study on small angle X-ray scattering patterns of intact vancomycin susceptible and non-susceptible Staphylococcus aureus cells

GlmS plays a key role in the virulence factor expression and biofilm formation ability of Staphylococcus aureus promoted by advanced glycation end products

C-di-AMP levels modulateStaphylococcus aureuscell wall thickness as well as virulence and contribute to antibiotic resistance and tolerance

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