scholarly journals Small-Colony Variant Selection as a Survival Strategy for Staphylococcus aureus in the Presence of Pseudomonas aeruginosa

2009 ◽  
Vol 75 (21) ◽  
pp. 6910-6912 ◽  
Author(s):  
Lalitha Biswas ◽  
Raja Biswas ◽  
Martin Schlag ◽  
Ralph Bertram ◽  
Friedrich Götz

ABSTRACT Previously it has been demonstrated that Staphylococcus aureus is sensitive toward Pseudomonas-secreted exotoxins, which preferentially target the electron transport chain in staphylococci. Here it is shown that a subpopulation of S. aureus survives these respiratory toxins of P seudomonas aeruginosa by selection of the small-colony variant (SCV) phenotype. Purified pyocyanin alone causes the same effect. A hem B mutant of S. aureus survives cocultivation with P. aeruginosa without a decrease in CFU.

2019 ◽  
Vol 74 (9) ◽  
pp. 2657-2665 ◽  
Author(s):  
Justin R Lenhard ◽  
Nicholas M Smith ◽  
Christine D Quach ◽  
Tuan Q Nguyen ◽  
Linh H Doan ◽  
...  

Abstract Objectives The optimal selection of antibacterials during polymicrobial infections is poorly defined. The objective of the current investigation was to quantify the pharmacodynamics of relevant antimicrobials during co-culture of Pseudomonas aeruginosa with two separate Staphylococcus aureus phenotypes. Methods Time–kill experiments were conducted against co-cultures of the P. aeruginosa strain PA01 paired with either the normal phenotype (NP) MRSA isolate COL or the small colony variant phenotype (SCVP) MRSA isolate Ia48. The killing by levofloxacin, gentamicin, clindamycin, vancomycin and polymyxin B was evaluated to investigate drugs with activity against one or both pathogens. A Hill-type function and a mechanism-based model were used to describe bacterial killing. Results P. aeruginosa attenuated the activity of clindamycin against NP MRSA, with a reduction in the Emax (maximal killing) from 3.67 (95% CI 2.79–4.56) in monoculture to 1.86 (95% CI 1.35–2.37) during co-culture, whereas a significant protective effect was not observed for other antibacterials. The reduction in NP MRSA killing by clindamycin was described well by a mechanism-based model that generated a maximal killing rate constant of clindamycin against the susceptible NP MRSA subpopulation of 0.267 h−1 in monoculture and 0.0395 h−1 in the presence of P. aeruginosa. During exposure to gentamicin, P. aeruginosa was the dominant organism in co-culture experiments regardless of the drug concentration or S. aureus phenotype; however, the SCVP MRSA was able to dominate the joint population beginning at a levofloxacin concentration of 1.5 mg/L. Conclusions The anti-staphylococcal activity of clindamycin was attenuated by the presence of P. aeruginosa.


2002 ◽  
Vol 70 (10) ◽  
pp. 5428-5437 ◽  
Author(s):  
Pierre Vaudaux ◽  
Patrice Francois ◽  
Carmelo Bisognano ◽  
William L. Kelley ◽  
Daniel P. Lew ◽  
...  

ABSTRACT Small colony variants (SCVs) of Staphylococcus aureus are slow-growing subpopulations that cause persistent and relapsing infections. The altered phenotype of SCV can arise from defects in menadione or hemin biosynthesis, which disrupt the electron transport chain and decrease ATP concentrations. With SCVs, virulence is altered by a decrease in exotoxin production and susceptibility to various antibiotics, allowing their intracellular survival. The expression of bacterial adhesins by SCVs is poorly documented. We tested fibrinogen- and fibronectin-mediated adhesion of a hemB mutant of S. aureus 8325-4 that is defective for hemin biosynthesis and exhibits a complete SCV phenotype. In this strain, adhesion to fibrinogen and fibronectin was significantly higher than that of its isogenic, normally growing parent and correlated with the increased surface display of these adhesins as assessed by flow cytometry. Real-time quantitative reverse transcription-PCR demonstrated increased expression of clfA and fnb genes by the hemB mutant compared to its isogenic parent. The influence of the hemB mutation on altered adhesin expression was confirmed by showing complete restoration of the wild-type adhesive phenotype in the hemB mutant, either by complementing with intact hemB or by supplementing the growth medium with hemin. Increased surface display of fibrinogen and fibronectin adhesins by the hemB mutation occurred independently from agr, a major regulatory locus of virulence factors in S. aureus. Both agr-positive and agr-lacking hemB mutants were also more efficiently internalized by human embryonic kidney cells than were their isogenic controls, presumably because of increased surface display of their fibronectin adhesins.


1993 ◽  
Vol 289 (1) ◽  
pp. 173-178 ◽  
Author(s):  
P Reichmann ◽  
H Görisch

In cells of Pseudomonas aeruginosa A.T.C.C. 17933 grown on ethanol the synthesis of a soluble c-type cytochrome, together with quinoprotein ethanol dehydrogenase, is induced. The cytochrome, with an alpha-absorption band at 550 nm, was purified to homogeneity. The molecular mass of the monomeric protein is 15 kDa, the pI is 4.8, and it contains one haem prosthetic group. The midpoint potential of the autoxidizable, but not autoreducible, cytochrome is 280 mV. Cytochrome c550 mediates electron transfer between quinoprotein ethanol dehydrogenase and ferricyanide. In a system composed of membrane particles with NN‘NN’-tetramethyl-p-phenylenediamine oxidase activity and quinoprotein ethanol dehydrogenase, oxygen consumption is only observed in the presence of cytochrome c550. This indicates the participation of the cytochrome in the electron-transport chain linked to quinoprotein ethanol dehydrogenase in P. aeruginosa. The electron transport from ethanol dehydrogenase to oxygen is inhibited by myxothiazol and antimycin, indicating that a cytochrome bc1-like complex is involved.


1968 ◽  
Vol 14 (6) ◽  
pp. 661-666 ◽  
Author(s):  
G. J. Leahy ◽  
D. J Currie ◽  
H. L. Holmes ◽  
J. R. Maltman

Growth-inhibitory activities of some or all of 98 1,4-naphthoquinones and 16 related compounds on Escherichia coli and two strains of Staphylococcus aureus were determined alone or in combination. These values, when plotted against their polarographic half-wave potentials and those of their C2-n-butylthio analogs support the hypothesis that these compounds, or the products resulting from their reaction with a protein nucleophile, function by short-circuiting one or other of the quinones present in the electron-transport chain.


mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Neal D. Hammer ◽  
Lici A. Schurig-Briccio ◽  
Svetlana Y. Gerdes ◽  
Robert B. Gennis ◽  
Eric P. Skaar

ABSTRACTStaphylococcus aureusis the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability ofS. aureusto cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (otype,bdtype, andaa3type), the genome contains genes encoding only two respiratory oxygen reductases,cydABandqoxABCD. Previous investigation showed thatcydABandqoxABCDare required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of thecydABandqoxABCDin virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is anaa3-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as abo3-type menaquinol oxidase. However, thebo3form of QoxABCD restricts the carbon sources that can support the growth ofS. aureus. In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiringFirmicutes. In total, these studies establish the heme A biosynthesis pathway inS. aureus, determine that QoxABCD is a typeaa3menaquinol oxidase, and reveal CtaM as a new protein required for typeaa3menaquinol oxidase function in multiple bacterial genera.IMPORTANCEStaphylococcus aureusrelies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of theS. aureuselectron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain ofS. aureusis comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration.


2014 ◽  
Vol 82 (10) ◽  
pp. 4337-4347 ◽  
Author(s):  
Vera Pader ◽  
Ellen H. James ◽  
Kimberley L. Painter ◽  
Sivaramesh Wigneshweraraj ◽  
Andrew M. Edwards

ABSTRACTStaphylococcus aureusis responsible for numerous chronic and recurrent infections, which are frequently associated with the emergence of small-colony variants (SCVs) that lack a functional electron transport chain. SCVs exhibit enhanced expression of fibronectin-binding protein (FnBP) and greatly reduced hemolysin production, although the basis for this is unclear. One hypothesis is that these phenotypes are a consequence of the reduced Agr activity of SCVs, while an alternative is that the lack of a functional electron transport chain and the resulting reduction in ATP production are responsible. Disruption of the electron transport chain ofS. aureusgenetically (hemBandmenD) or chemically, using 2-n-heptyl-4-hydroxyquinolineN-oxide (HQNO), inhibited both growth and Agr activity and conferred an SCV phenotype. Supplementation of the culture medium with synthetic autoinducing peptide (sAIP) significantly increased Agr expression in bothhemBmutant strains andS. aureusgrown with HQNO and significantly reduced staphylococcal adhesion to fibronectin. However, sAIP did not promote hemolysin expression inhemBmutant strains orS. aureusgrown with HQNO. Therefore, while Agr regulates fibronectin binding in SCVs, it cannot promote hemolysin production in the absence of a functional electron transport chain.


2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Kimberley L. Painter ◽  
Alex Hall ◽  
Kam Pou Ha ◽  
Andrew M. Edwards

ABSTRACT Small-colony variants (SCVs) of Staphylococcus aureus typically lack a functional electron transport chain and cannot produce virulence factors such as leukocidins, hemolysins, or the antioxidant staphyloxanthin. Despite this, SCVs are associated with persistent infections of the bloodstream, bones, and prosthetic devices. The survival of SCVs in the host has been ascribed to intracellular residency, biofilm formation, and resistance to antibiotics. However, the ability of SCVs to resist host defenses is largely uncharacterized. To address this, we measured the survival of wild-type and SCV S. aureus in whole human blood, which contains high numbers of neutrophils, the key defense against staphylococcal infection. Despite the loss of leukocidin production and staphyloxanthin biosynthesis, SCVs defective for heme or menaquinone biosynthesis were significantly more resistant to the oxidative burst than wild-type bacteria in human blood or the presence of purified neutrophils. Supplementation of the culture medium of the heme-auxotrophic SCV with heme, but not iron, restored growth, hemolysin and staphyloxanthin production, and sensitivity to the oxidative burst. Since Enterococcus faecalis is a natural heme auxotroph and cause of bloodstream infection, we explored whether restoration of the electron transport chain in this organism also affected survival in blood. Incubation of E. faecalis with heme increased growth and restored catalase activity but resulted in decreased survival in human blood via increased sensitivity to the oxidative burst. Therefore, the lack of functional electron transport chains in SCV S. aureus and wild-type E. faecalis results in reduced growth rate but provides resistance to a key immune defense mechanism.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Hussein A Kadhum ◽  
Thualfakar H Hasan2

The study involved the selection of two isolates from Bacillus subtilis to investigate their inhibitory activity against some bacterial pathogens. B sub-bacteria were found to have a broad spectrum against test bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. They were about 23-30 mm and less against Klebsiella sp. The sensitivity of some antibodies was tested on the test samples. The results showed that the inhibitory ability of bacterial growth in the test samples using B. subtilis extract was more effective than the antibiotics used.


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