Resistance to oxidative stress by inner membrane protein ElaB is regulated by OxyR and RpoS

Guo, Yunxue; Li, Yangmei; Zhan, Wu; Wood, Thomas K.; Wang, Pengxia

doi:10.1111/1751-7915.13369

Cited by 21 publications

(16 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oxidative state plays an important role in cell integrity and function, including bacteria [51,52]. We show here that the NAC application to P. aeruginosa biofilm in our in vitro wound biofilm system leads to a reduced ratio of NAD + / NADH inside the bacteria, indicating high levels of oxidative stress [53].…”

mentioning

confidence: 63%

N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

Jane

et al. 2020

Journal of Diabetes Research

View full text Add to dashboard Cite

Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with α-tocopherol, N-acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS). We hypothesize that NAC creates a microenvironment that affects bacterial survival and EPS integrity. To test this hypothesis, we developed an in vitro biofilm system using microbiome taken directly from diabetic mouse chronic wounds. For these studies, we chose mice in which chronic wound microbiome was rich in Pseudomonas aeruginosa (97%). We show that NAC at concentrations with pH < pKa causes bacterial cell death and breakdown of EPS. When used before biofilm is formed, NAC leads to bacterial cell death whereas treatment after the biofilm is established NAC causes biofilm dismantling accompanied by bacterial cell death. Mechanistically, we show that NAC can penetrate the bacterial membrane, increase oxidative stress, and halt protein synthesis. We also show that low pH is important for the actions of NAC and that bacterial death occurs independently of the presence of biofilm. In addition, we show that both the acetyl and carboxylic groups play key roles in NAC functions. The results presented here provide insight into the mechanisms by which NAC dismantles biofilm and how it could be used to treat chronic wounds after debridement (NAC applied at the start of culture) or without debridement (NAC applied when biofilm is already formed). This approach can be taken to develop biofilm from microbiome taken directly from human chronic wounds to test molecules that could be effective for the treatment of specific biofilm compositions.

show abstract

mentioning

confidence: 63%

N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

Jane

et al. 2020

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…The C-tail anchored inner membrane protein ElaB was recently shown to protect bacteria against oxidative stress and heat shock and its expression to be co-ordinately regulated by both RpoS and OxyR (23). Transcription of elaB was strongly upregulated in three of four tested L-forms and appeared to be associated with upregulation of rpoS but not oxyR (in which no significant changes were seen) (23).…”

Section: Resultsmentioning

confidence: 99%

L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli

Kamruzzaman

Martínez-Martín

et al. 2021

Preprint

View full text Add to dashboard Cite

The bacterial L-form is induced by exposure to cell wall targeting antibiotics or innate immune effectors such as lysozyme and is likely to be important in many human infections. Here, we demonstrate that the osmotically fragile L-form is a distinct physiological state in Escherichia coli that is highly tolerant of oxidative stress and resistant to powerful antibiotics and common therapeutic bacteriophages. L-forms quickly revert (<20h) to their cell-walled state after antibiotic withdrawal, with apparently normal physiology and with few or no changes in DNA sequence. T4-like phages that are obligately lytic in cell-walled E. coli preferentially pseudolysogenise their L-forms providing them with transient superinfection immunity. Our data indicate that L-form switching is a common response of pathogenic E. coli strains to cell wall-targeting antibiotics and that the most commonly used lytic bacteriophages are ineffective against them in this state.

show abstract

“…Eight and five of the proteins were upregulated and downregulated due to the deletion of spr , respectively. The functions of some of these proteins are involved in bacterial motility (FliC; Lane et al, 2005 ), cell shape maintenance, envelope integrity (ElaB, SlyB, and YhcB; Plesa et al, 2006 ; Li et al, 2012 ; Guo et al, 2019 ), and peptidoglycan biogenesis (YceG; Yunck et al, 2016 ), suggesting that Spr deficiency may interfere with these functions. Since bacterial motility, morphological switching, and envelope integrity have been shown to be required for virulence of UPEC ( Horvath et al, 2011 ; Flores-Mireles et al, 2015 ; Hews et al, 2019 ), the attenuated ability of ∆ spr -UTI89 to cause UTI may be due to the altered envelope characteristics.…”

Section: Resultsmentioning

confidence: 99%

Peptidoglycan Endopeptidase Spr of Uropathogenic Escherichia coli Contributes to Kidney Infections and Competitive Fitness During Bladder Colonization

et al. 2020

View full text Add to dashboard Cite

Uropathogenic Escherichia coli (UPEC) is the most common pathogen of urinary tract infections (UTIs). Antibiotic therapy is the conventional measure to manage such infections. However, the rapid emergence of antibiotic resistance has reduced the efficacy of antibiotic treatment. Given that the bacterial factors required for the full virulence of the pathogens are potential therapeutic targets, identifying such factors may facilitate the development of novel therapeutic strategies against UPEC UTIs. The peptidoglycan (PG) endopeptidase Spr (also named MepS) is required for PG biogenesis in E. coli. In the present study, we found that Spr deficiency attenuated the ability of UPEC to infect kidneys and induced a fitness defect during bladder colonization in a mouse model of UTI. Based on the liquid chromatography (LC)/mass spectrometry (MS)/MS analysis of the bacterial envelope, spr deletion changed the levels of some envelope-associated proteins, suggesting that Spr deficiency interfere with the components of the bacterial structure. Among the proteins, FliC was significantly downregulated in the spr mutant, which is resulted in reduced motility. Lack of Spr might hinder the function of the flagellar transcriptional factor FlhDC to decrease FliC expression. The motility downregulation contributed to the reduced fitness in urinary tract colonization. Additionally, spr deletion compromised the ability of UPEC to evade complement-mediated attack and to resist intracellular killing of phagocytes, consequently decreasing UPEC bloodstream survival. Spr deficiency also interfered with the UPEC morphological switch from bacillary to filamentous shapes during UTI. It is known that bacterial filamentation protects UPEC from phagocytosis by phagocytes. In conclusion, Spr deficiency was shown to compromise multiple virulence properties of UPEC, leading to attenuation of the pathogen in urinary tract colonization and bloodstream survival. These findings indicate that Spr is a potential antimicrobial target for further studies attempting to develop novel strategies in managing UPEC UTIs.

show abstract

Resistance to oxidative stress by inner membrane protein ElaB is regulated by OxyR and RpoS

Cited by 21 publications

References 52 publications

N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli

Peptidoglycan Endopeptidase Spr of Uropathogenic Escherichia coli Contributes to Kidney Infections and Competitive Fitness During Bladder Colonization

Contact Info

Product

Resources

About