scholarly journals EttA is likely non-essential in Staphylococcus aureus persistence, fitness or resistance to antibiotics

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Michal Meir ◽  
Anna Rozenblit ◽  
Simona Fliger ◽  
Yuval Geffen ◽  
Daniel Barkan
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Growth Phase ◽  
Cell Formation ◽  
Stationary Growth Phase ◽  
Clinical Isolates ◽  
Beta Lactam ◽  
Stationary Growth ◽  
Mechanisms Of Persistence

Abstract Background Tolerance to antibiotics and persistence are associated with antibiotic treatment failures, chronic-relapsing infections, and emerging antibiotic resistance in various bacteria, including Staphylococcus aureus. Mechanisms of persistence are largely unknown, yet have been linked to physiology under low-ATP conditions and the metabolic-inactive state. EttA is an ATP-binding cassette protein, linked in Eschrechia coli to ribosomal hibernation and fitness in stationary growth phase, yet its role in S. aureus physiology is unknown. Results Using whole genome sequencing (WGS) of serial clinical isolates, we identified an EttA-negative S. aureus mutant (ettAstop), and its isogenic wild-type counterpart. We used these two isogenic clones to investigate the role of ettA in S. aureus physiology in starvation and antibiotic stress, and test its role in persistence and antibiotic tolerance. ettAstop and its WT counterpart were similar in their antibiotic resistance profiles to multiple antibiotics. Population dynamics of ettAstop and the WT were similar in low-nutrient setting, with similar recovery from stationary growth phase or starvation. Supra-bacteriocidal concentration of cefazolin had the same killing effect on ettAstop and WT populations, with no difference in persister formation. Conclusions Lack of ettA does not affect S. aureus antibiotic resistance, beta-lactam tolerance, resilience to starvation or fitness following starvation. We conclude the role of ettA in S. aureus physiology is limited or redundant with another, unidentified gene. WGS of serial clinical isolates may enable investigation of other single genes involved in S. aureus virulence, and specifically persister cell formation.

scholarly journals Two Novel Semisynthetic Lipoglycopeptides Active against Staphylococcus aureus Biofilms and Cells in Late Stationary Growth Phase

2021 ◽  
Vol 14 (11) ◽  
pp. 1182
Author(s):  
Vladimir Vimberg ◽  
Leona Zieglerova ◽  
Aninda Mazumdar ◽  
Zsolt Szűcs ◽  
Aniko Borbás ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Growth Phase ◽  
Stationary Growth Phase ◽  
Glycopeptide Antibiotics ◽  
Stationary Growth ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
New Antibiotics

The increase in antibiotic resistance among Gram-positive bacteria underscores the urgent need to develop new antibiotics. New antibiotics should target actively growing susceptible bacteria that are resistant to clinically accepted antibiotics including bacteria that are not growing or are protected in a biofilm environment. In this paper, we compare the in vitro activities of two new semisynthetic glycopeptide antibiotics, MA79 and ERJ390, with two clinically used glycopeptide antibiotics—vancomycin and teicoplanin. The new antibiotics effectively killed not only exponentially growing cells of Staphylococcus aureus, but also cells in the stationary growth phase and biofilm.

scholarly journals The CiaRH System of Streptococcus pneumoniae Prevents Lysis during Stress Induced by Treatment with Cell Wall Inhibitors and by Mutations in pbp2x Involved in β-Lactam Resistance

2006 ◽  
Vol 188 (5) ◽  
pp. 1959-1968 ◽  
Author(s):  
Thorsten Mascher ◽  
Manuel Heintz ◽  
Dorothea Zähner ◽  
Michelle Merai ◽  
Regine Hakenbeck
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Growth Phase ◽  
Point Mutations ◽  
Normal Growth ◽  
Stationary Growth Phase ◽  
Clinical Isolates ◽  
Loss Of Function ◽  
Beta Lactam ◽  
Stationary Growth

ABSTRACT The two-component signal-transducing system CiaRH of Streptococcus pneumoniae plays an important role during the development of beta-lactam resistance in laboratory mutants. We show here that a functional CiaRH system is required for survival under many different lysis-inducing conditions. Mutants with an activated CiaRH system were highly resistant to lysis induced by a wide variety of early and late cell wall inhibitors, such as cycloserine, bacitracin, and vancomycin, and were also less susceptible to these drugs. In contrast, loss-of-function CiaRH mutants were hypersusceptible to these drugs and were apparently unable to maintain a stationary growth phase in normal growth medium and under choline deprivation as well. Moreover, disruption of CiaR in penicillin-resistant mutants with an altered pbp2x gene encoding low-affinity PBP2x resulted in severe growth defects and rapid lysis. This phenotype was observed with pbp2x genes containing point mutations selected in the laboratory and with highly altered mosaic pbp2x genes from penicillin-resistant clinical isolates as well. This documents for the first time that PBP2x mutations required for development of beta-lactam resistance are functionally not neutral and are tolerated only in the presence of the CiaRH system. This might explain why cia mutations have not been observed in penicillin-resistant clinical isolates. The results document that the CiaRH system is required for maintenance of the stationary growth phase and for prevention of autolysis triggered under many different conditions, suggesting a major role for this system in ensuring cell wall integrity.

The Effect of Adding Blood on the Virulence Genes Expression of Staphylococcus aureus in Exponential and Stationary Growth Phase

2017 ◽  
Vol 10 (6) ◽  
Author(s):  
Hadi Koohsari ◽  
Ezzat Allah Ghaemi ◽  
Noor Amir Mozaffari ◽  
Abdolvahhab Moradi ◽  
Maryam Sadegh-Sheshpoli ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Growth Phase ◽  
Virulence Genes ◽  
Stationary Growth Phase ◽  
Stationary Growth ◽  
Genes Expression

scholarly journals Clostridioides difficile Phosphoproteomics Shows an Expansion of Phosphorylated Proteins in Stationary Growth Phase

mSphere ◽  
2022 ◽  
Author(s):  
Wiep Klaas Smits ◽  
Yassene Mohammed ◽  
Arnoud H. de Ru ◽  
Valentina Cordo' ◽  
Annemieke H. Friggen ◽  
...  
Keyword(s):  
Growth Phase ◽  
Posttranslational Modification ◽  
Stationary Growth Phase ◽  
Comprehensive Analysis ◽  
Limited Evidence ◽  
Stationary Growth ◽  
Content Type ◽  
Phosphorylated Proteins ◽  
Clostridioides Difficile

In this paper, we present a comprehensive analysis of protein phosphorylation in the Gram-positive enteropathogen Clostridioides difficile . To date, only limited evidence on the role of phosphorylation in the regulation of this organism has been published; the current study is expected to form the basis for research on this posttranslational modification in C. difficile .  

scholarly journals Biological Approach to Modeling of Staphylococcus aureus High-Hydrostatic-Pressure Inactivation Kinetics

2010 ◽  
Vol 76 (21) ◽  
pp. 6982-6990 ◽  
Author(s):  
Guillermo Cebrián ◽  
Chris W. Michiels ◽  
Pilar Mañas ◽  
Santiago Condón
Keyword(s):  
Staphylococcus Aureus ◽  
Sodium Chloride ◽  
Hydrostatic Pressure ◽  
Growth Phase ◽  
High Hydrostatic Pressure ◽  
Stationary Growth Phase ◽  
Inactivation Rate ◽  
Inactivation Kinetics ◽  
Stationary Growth ◽  
Tail Region

ABSTRACT Graphs for survival under high hydrostatic pressure (450 MPa; 25°C; citrate-phosphate buffer, pH 7.0) of stationary-growth-phase cells of eight Staphylococcus aureus strains were found to be nonlinear. The strains could be classified into two groups on the basis of the shoulder length. Some of them showed long shoulders of up to 20 min at 450 MPa, while others had shoulders of <3.5 min. All strains showed tails. No significant differences in the inactivation rate were found during the log-linear death phase among the eight strains. The entry into stationary growth phase resulted both in an increase in shoulder length and in a decrease in the inactivation rate. However, whereas shoulder length proved to depend on sigma B factor activity, the inactivation rate did not. Recovery in anaerobiosis decreased the inactivation rate but did not affect the shoulder length. Addition of the minimum noninhibitory concentration of sodium chloride to the recovery medium resulted in a decrease in shoulder length and in an increase in the inactivation rate for stationary-growth-phase cells. In the tail region, up to 90% of the population remained sensitive to sodium chloride.

scholarly journals Role of the Stationary Growth Phase Sigma Factor RpoS of Burkholderia pseudomallei in Response to Physiological Stress Conditions

2003 ◽  
Vol 185 (23) ◽  
pp. 7008-7014 ◽  
Author(s):  
Benchamas Subsin ◽  
Mark S. Thomas ◽  
Gerd Katzenmeier ◽  
Jonathan G. Shaw ◽  
Sumalee Tungpradabkul ◽  
...  
Keyword(s):  
Growth Phase ◽  
Sigma Factor ◽  
Burkholderia Pseudomallei ◽  
Physiological Stress ◽  
Stationary Growth Phase ◽  
Null Mutant ◽  
Stationary Growth ◽  
Increased Sensitivity ◽  
And Oxidative Stress

ABSTRACT The Burkholderia pseudomallei rpoS gene was identified, and an rpoS null mutant was constructed. The mutant was shown to have an increased sensitivity to carbon starvation and oxidative stress. By using rpoS-lacZ fusions, transcription of rpoS was shown to be growth phase regulated, reaching a peak upon entry into stationary phase.

scholarly journals Role of LmeA, a Mycobacterial Periplasmic Protein, in Maintaining the Mannosyltransferase MptA and Its Product Lipomannan under Stress

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Kathryn C. Rahlwes ◽  
Sarah H. Osman ◽  
Yasu S. Morita
Keyword(s):  
Growth Phase ◽  
Molecular Mechanisms ◽  
Cell Envelope ◽  
Stationary Growth Phase ◽  
Cellular Level ◽  
Nutrient Starvation ◽  
Stress Conditions ◽  
Periplasmic Protein ◽  
Stationary Growth

ABSTRACT The mycobacterial cell envelope has a diderm structure, composed of an outer mycomembrane, an arabinogalactan-peptidoglycan cell wall, a periplasm, and an inner membrane. Lipomannan (LM) and lipoarabinomannan (LAM) are structural and immunomodulatory components of this cell envelope. LM/LAM biosynthesis involves a number of mannosyltransferases and acyltransferases, and MptA is an α1,6-mannosyltransferase involved in the final extension of the mannan chain. Recently, we reported the periplasmic protein LmeA being involved in the maturation of the mannan backbone in Mycobacterium smegmatis. Here, we examined the role of LmeA under stress conditions. We found that lmeA transcription was upregulated under two stress conditions: stationary growth phase and nutrient starvation. Under both conditions, LAM was decreased, but LM was relatively stable, suggesting that maintaining the cellular level of LM under stress is important. Surprisingly, the protein levels of MptA were decreased in an lmeA deletion (ΔlmeA) mutant under both stress conditions. The transcript levels of mptA in the ΔlmeA mutant were similar to or even higher than those in the wild type, indicating that the decrease of MptA protein was a posttranscriptional event. The ΔlmeA mutant was unable to maintain the cellular level of LM under stress, consistent with the decrease in MptA. Even during active growth, overexpression of LmeA led the cells to produce more LM and become more resistant to several antibiotics. Altogether, our study reveals the roles of LmeA in the homeostasis of the MptA mannosyltransferase, particularly under stress conditions, ensuring the stable expression of LM and the maintenance of cell envelope integrity. IMPORTANCE Mycobacteria differentially regulate the cellular amounts of lipoglycans in response to environmental changes, but the molecular mechanisms of this regulation remain unknown. Here, we demonstrate that cellular lipoarabinomannan (LAM) levels rapidly decline under two stress conditions, stationary growth phase and nutrient starvation, while the levels of another related lipoglycan, lipomannan (LM), stay relatively constant. The persistence of LM under stress correlated with the maintenance of two key mannosyltransferases, MptA and MptC, in the LM biosynthetic pathway. We further showed that the stress exposures lead to the upregulation of lmeA gene expression and that the periplasmic protein LmeA plays a key role in maintaining the enzyme MptA and its product LM under stress conditions. These findings reveal new aspects of how lipoglycan biosynthesis is regulated under stress conditions in mycobacteria.

scholarly journals Efficacy of Daptomycin in Implant-Associated Infection Due to Methicillin-Resistant Staphylococcus aureus: Importance of Combination with Rifampin

2009 ◽  
Vol 53 (7) ◽  
pp. 2719-2724 ◽  
Author(s):  
Anne-Kathrin John ◽  
Daniela Baldoni ◽  
Manuel Haschke ◽  
Katharina Rentsch ◽  
Patrick Schaerli ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Growth Phase ◽  
Treatment Options ◽  
Stationary Growth Phase ◽  
Infection Model ◽  
Logarithmic Phase ◽  
High Dose ◽  
Cure Rate ◽  
Stationary Growth ◽  
Time Kill

ABSTRACT Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 μg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 μg/ml, daptomycin reduced the counts by >3 log10 CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 μg/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log10 CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log10 CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

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