scholarly journals Strain Background, Species Frequency, and Environmental Conditions Are Important in Determining Pseudomonas aeruginosa and Staphylococcus aureus Population Dynamics and Species Coexistence

2020 ◽  
Vol 86 (18) ◽  
Author(s):  
Selina Niggli ◽  
Rolf Kümmerli
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Population Dynamics ◽  
Environmental Conditions ◽  
Species Coexistence ◽  
Content Type ◽  
Species Frequency ◽  
Culturing Conditions ◽  
Polymicrobial Infections ◽  
Strain Background

ABSTRACT Bacterial communities in the environment and in infections are typically diverse, yet we know little about the factors that determine interspecies interactions. Here, we apply concepts from ecological theory to understand how biotic and abiotic factors affect interaction patterns between the two opportunistic human pathogens Pseudomonas aeruginosa and Staphylococcus aureus, which often cooccur in polymicrobial infections. Specifically, we conducted a series of short- and long-term competition experiments between P. aeruginosa PAO1 (as our reference strain) and three different S. aureus strains (Cowan I, 6850, and JE2) at three starting frequencies and under three environmental (culturing) conditions. We found that the competitive ability of P. aeruginosa strongly depended on the strain background of S. aureus, whereby P. aeruginosa dominated against Cowan I and 6850 but not against JE2. In the latter case, both species could end up as winners depending on conditions. Specifically, we observed strong frequency-dependent fitness patterns, including positive frequency dependence, where P. aeruginosa could dominate JE2 only when common (not when rare). Finally, changes in environmental (culturing) conditions fundamentally altered the competitive balance between the two species in a way that P. aeruginosa dominance increased when moving from shaken to static environments. Altogether, our results highlight that ecological details can have profound effects on the competitive dynamics between coinfecting pathogens and determine whether two species can coexist or invade each others’ populations from a state of rare frequency. Moreover, our findings might parallel certain dynamics observed in chronic polymicrobial infections. IMPORTANCE Bacterial infections are frequently caused by more than one species, and such polymicrobial infections are often considered more virulent and more difficult to treat than the respective monospecies infections. Pseudomonas aeruginosa and Staphylococcus aureus are among the most important pathogens in polymicrobial infections, and their cooccurrence is linked to worse disease outcome. There is great interest in understanding how these two species interact and what the consequences for the host are. While previous studies have mainly looked at molecular mechanisms implicated in interactions between P. aeruginosa and S. aureus, here we show that ecological factors, such as strain background, species frequency, and environmental conditions, are important elements determining population dynamics and species coexistence patterns. We propose that the uncovered principles also play major roles in infections and, therefore, proclaim that an integrative approach combining molecular and ecological aspects is required to fully understand polymicrobial infections.

scholarly journals Strain background, species frequency and environmental conditions are important in determining population dynamics and species co-existence between Pseudomonas aeruginosa and Staphylococcus aureus

2020 ◽  
Author(s):  
Selina Niggli ◽  
Rolf Kümmerli
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Population Dynamics ◽  
Environmental Conditions ◽  
Integrative Approach ◽  
Interaction Patterns ◽  
Species Frequency ◽  
Staphyloccocus Aureus ◽  
Culturing Conditions ◽  
Polymicrobial Infections ◽  
Strain Background

AbstractBacterial communities in the environment and in infections are typically diverse, yet we know little about the factors that determine interspecies interactions. Here, we apply concepts from ecological theory to understand how biotic and abiotic factors affect interaction patterns between the two opportunistic human pathogens Pseudomonas aeruginosa and Staphyloccocus aureus, which often co-occur in polymicrobial infections. Specifically, we conducted a series of short- and long-term competition experiments between P. aeruginosa PAO1 (as our reference strain) and three different S. aureus strains (Cowan I, 6850, JE2) at three starting frequencies and under three environmental (culturing) conditions. We found that the competitive ability of P. aeruginosa strongly depended on the strain background of S. aureus, whereby P. aeruginosa dominated against Cowan I and 6850, but not against JE2. In the latter case, both species could end up as winners depending on conditions. Specifically, we observed strong frequency-dependent fitness patterns, including positive frequency dependence, where P. aeruginosa could dominate JE2 only when common, but not when rare. Finally, changes in environmental (culturing) conditions fundamentally altered the competitive balance between the two species, in a way that P. aeruginosa dominance increased when moving from shaken to static environments. Altogether, our results highlight that ecological details can have profound effects on the competitive dynamics between co-infecting pathogens, and determine whether two species can co-exist or invade each others’ populations from rare. Moreover, our findings might parallel certain dynamics observed in chronic polymicrobial infections.ImportanceBacterial infections are frequently caused by more than one species and such polymicrobial infections are often considered more virulent and more difficult to treat than the respective monospecies infections. Pseudomonas aeruginosa and Staphyloccocus aureus are among the most important pathogens in polymicrobial infections and their co-occurrence is linked to worse disease outcome. There is great interest in understanding how these two species interact with each other and what the consequences for the host are. While previous studies have mainly looked at molecular mechanisms implicated in interactions between P. aeruginosa and S. aureus, here we show that ecological factors such as strain background, species frequency and environmental conditions are important elements determining population dynamics and species co-existence patterns. We propose that the uncovered principles may also play major roles in infections, and therefore proclaim that an integrative approach combining molecular and ecological aspects is required to fully understand polymicrobial infections.

scholarly journals Multiple Compounds Secreted by Pseudomonas aeruginosa Increase the Tolerance of Staphylococcus aureus to the Antimicrobial Metals Copper and Silver

mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Nadia K. Monych ◽  
Raymond J. Turner
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Chemical Communication ◽  
Single Species ◽  
Species Group ◽  
Chronic Infections ◽  
Content Type ◽  
Alternative Antimicrobials ◽  
Polymicrobial Infections

Alternative antimicrobials, such as metals, are one of the methods currently used to help mitigate antibiotic resistance. Metal-based antimicrobials such as copper and silver are used currently both to prevent and to treat infections. Although the efficacy of these antimicrobials has been determined in single-species culture, bacteria rarely exist in a single-species group in the environment. Both Pseudomonas aeruginosa and Staphylococcus aureus are often found associated with each other in severe chronic infections displaying increased virulence and antibiotic tolerance. In this study, we determined that multiple compounds secreted by P. aeruginosa are able to increase the tolerance of S. aureus to both copper and silver. This work demonstrates the expansive chemical communication occurring in polymicrobial infections between bacteria.

scholarly journals Iron Depletion Enhances Production of Antimicrobials by Pseudomonas aeruginosa

2015 ◽  
Vol 197 (14) ◽  
pp. 2265-2275 ◽  
Author(s):  
Angela T. Nguyen ◽  
Jace W. Jones ◽  
Max A. Ruge ◽  
Maureen A. Kane ◽  
Amanda G. Oglesby-Sherrouse
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Iron Depletion ◽  
Content Type ◽  
Regulatory Pathways ◽  
Enhanced Production ◽  
Antimicrobial Metabolites ◽  
Polymicrobial Infections

ABSTRACTCystic fibrosis (CF) is a heritable disease characterized by chronic, polymicrobial lung infections. WhileStaphylococcus aureusis the dominant lung pathogen in young CF patients,Pseudomonas aeruginosabecomes predominant by adulthood.P. aeruginosaproduces a variety of antimicrobials that likely contribute to this shift in microbial populations. In particular, secretion of 2-alkyl-4(1H)-quinolones (AQs) contributes to lysis ofS. aureusin coculture, providing an iron source toP. aeruginosabothin vitroandin vivo. We previously showed that production of one such AQ, thePseudomonasquinolone signal (PQS), is enhanced by iron depletion and that this induction is dependent upon the iron-responsive PrrF small RNAs (sRNAs). Here, we demonstrate that antimicrobial activity againstS. aureusduring coculture is also enhanced by iron depletion, and we provide evidence that multiple AQs contribute to this activity. Strikingly, aP. aeruginosaΔprrFmutant, which produces very little PQS in monoculture, was capable of mediating iron-regulated growth suppression ofS. aureus. We show that the presence ofS. aureussuppresses the ΔprrF1,2mutant's defect in iron-regulated PQS production, indicating that a PrrF-independent iron regulatory pathway mediates AQ production in coculture. We further demonstrate that iron-regulated antimicrobial production is conserved in multipleP. aeruginosastrains, including clinical isolates from CF patients. These results demonstrate that iron plays a central role in modulating interactions ofP. aeruginosawithS. aureus. Moreover, our studies suggest that established iron regulatory pathways of these pathogens are significantly altered during polymicrobial infections.IMPORTANCEChronic polymicrobial infections involvingPseudomonas aeruginosaandStaphylococcus aureusare a significant cause of morbidity and mortality, as the interplay between these two organisms exacerbates infection. This is in part due to enhanced production of antimicrobial metabolites byP. aeruginosawhen these two species are cocultured. Using both established and newly developed coculture techniques, this report demonstrates that iron depletion increasesP. aeruginosa's ability to suppress growth ofS. aureus. These findings present a novel role for iron in modulating microbial interaction and provide the basis for understanding how essential nutrients drive polymicrobial infections.

scholarly journals Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Content Type

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

scholarly journals Simultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Ayesha Khan ◽  
William C. Shropshire ◽  
Blake Hanson ◽  
An Q. Dinh ◽  
Audrey Wanger ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Critically Ill Patient ◽  
Whole Genome ◽  
Candida Auris ◽  
Content Type ◽  
Simultaneous Infection ◽  
Polymicrobial Infections ◽  
Selection Of

ABSTRACT We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in a 56-year-old woman who received health care in India and was also colonized by Candida auris. A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.

scholarly journals Disruption of Cross-Feeding Inhibits Pathogen Growth in the Sputa of Patients with Cystic Fibrosis

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Jeffrey M. Flynn ◽  
Lydia C. Cameron ◽  
Talia D. Wiggen ◽  
Jordan M. Dunitz ◽  
William R. Harcombe ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Susceptibility ◽  
Susceptibility Testing ◽  
Anaerobic Bacteria ◽  
Content Type ◽  
Growth Environment ◽  
Polymicrobial Infections

ABSTRACT A critical limitation in the management of chronic polymicrobial infections is the lack of correlation between antibiotic susceptibility testing (AST) and patient responses to therapy. Underlying this disconnect is our inability to accurately recapitulate the in vivo environment and complex polymicrobial communities in vitro. However, emerging evidence suggests that, if modeled and tested accurately, interspecies relationships can be exploited by conventional antibiotics predicted to be ineffective by standard AST. As an example, under conditions where Pseudomonas aeruginosa relies on cocolonizing organisms for nutrients (i.e., cross-feeding), multidrug-resistant P. aeruginosa may be indirectly targeted by inhibiting the growth of its metabolic partners. While this has been shown in vitro using synthetic bacterial communities, the efficacy of a “weakest-link” approach to controlling host-associated polymicrobial infections has not yet been demonstrated. To test whether cross-feeding inhibition can be leveraged in clinically relevant contexts, we collected sputa from cystic fibrosis (CF) subjects and used enrichment culturing to isolate both P. aeruginosa and anaerobic bacteria from each sample. Predictably, both subpopulations showed various antibiotic susceptibilities when grown independently. However, when P. aeruginosa was cultured and treated under cooperative conditions in which it was dependent on anaerobic bacteria for nutrients, the growth of both the pathogen and the anaerobe was constrained despite their intrinsic antibiotic resistance profiles. These data demonstrate that the control of complex polymicrobial infections may be achieved by exploiting obligate or facultative interspecies relationships. Toward this end, in vitro susceptibility testing should evolve to more accurately reflect in vivo growth environments and microbial interactions found within them. IMPORTANCE Antibiotic efficacy achieved in vitro correlates poorly with clinical outcomes after treatment of chronic polymicrobial diseases; if a pathogen demonstrates susceptibility to a given antibiotic in the lab, that compound is often ineffective when administered clinically. Conversely, if a pathogen is resistant in vitro, patient treatment with that same compound can elicit a positive response. This discordance suggests that the in vivo growth environment impacts pathogen antibiotic susceptibility. Indeed, here we demonstrate that interspecies relationships among microbiotas in the sputa of cystic fibrosis patients can be targeted to indirectly inhibit the growth of Pseudomonas aeruginosa. The therapeutic implication is that control of chronic lung infections may be achieved by exploiting obligate or facultative relationships among airway bacterial community members. This strategy is particularly relevant for pathogens harboring intrinsic multidrug resistance and is broadly applicable to chronic polymicrobial airway, wound, and intra-abdominal infections.

scholarly journals Draft Genome Sequences of Two Pseudomonas aeruginosa Isolates from the Female Urogenital Tract

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Genevieve Johnson ◽  
Carine R. Mores ◽  
Alan J. Wolfe ◽  
Catherine Putonti
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Environmental Conditions ◽  
Draft Genome ◽  
Urogenital Tract ◽  
Negative Bacterium ◽  
Genome Sequences ◽  
Gram Negative ◽  
Content Type

Pseudomonas aeruginosa is a Gram-negative bacterium that has the ability to survive in and readily adapt to a variety of environmental conditions. Here, we report 2 genome sequences of P. aeruginosa strains, UMB1046 and UMB5686, isolated from the female urogenital tract.

scholarly journals Pseudomonas aeruginosa Alginate Benefits Staphylococcus aureus?

2020 ◽  
Vol 202 (8) ◽  
Author(s):  
Michael J. Schurr
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Cell Membrane ◽  
Membrane Integrity ◽  
Partial Explanation ◽  
Content Type ◽  
First Report ◽  
Cell Membrane Integrity ◽  
Link Type

ABSTRACT In this issue of Journal of Bacteriology, Price et al. show that the Pseudomonas aeruginosa-produced exopolysaccharide alginate protects Staphylococcus aureus by dampening the expression of P. aeruginosa virulence products that usually inhibit S. aureus respiration and cell membrane integrity when the two organisms compete in other environments (C. E. Price, D. G. Brown, D. H. Limoli, V. V. Phelan, and G. A. O’Toole, J Bacteriol 202:e00559-19, 2020, https://doi.org/10.1128/jb.00559-19). This is the first report that exogenously added alginate affects P. aeruginosa competition and provides a partial explanation for S. aureus and P. aeruginosa coinfections in cystic fibrosis.

scholarly journals d-Amino Acids Enhance the Activity of Antimicrobials against Biofilms of Clinical Wound Isolates of Staphylococcus aureus and Pseudomonas aeruginosa

2014 ◽  
Vol 58 (8) ◽  
pp. 4353-4361 ◽  
Author(s):  
Carlos J. Sanchez ◽  
Kevin S. Akers ◽  
Desiree R. Romano ◽  
Ronald L. Woodbury ◽  
Sharanda K. Hardy ◽  
...  
Keyword(s):  
Amino Acids ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Clinical Isolates ◽  
Chronic Infections ◽  
Content Type ◽  
Log Reduction ◽  
Viable Bacteria ◽  
Biofilm Bacteria

ABSTRACTWithin wounds, microorganisms predominantly exist as biofilms. Biofilms are associated with chronic infections and represent a tremendous clinical challenge. As antibiotics are often ineffective against biofilms, use of dispersal agents as adjunctive, topical therapies for the treatment of wound infections involving biofilms has gained interest. We evaluatedin vitrothe dispersive activity ofd-amino acids (d-AAs) on biofilms from clinical wound isolates ofStaphylococcus aureusandPseudomonas aeruginosa; moreover, we determined whether combinations ofd-AAs and antibiotics (clindamycin, cefazolin, oxacillin, rifampin, and vancomycin forS. aureusand amikacin, colistin, ciprofloxacin, imipenem, and ceftazidime forP. aeruginosa) enhance activity against biofilms.d-Met,d-Phe, andd-Trp at concentrations of ≥5 mM effectively dispersed preformed biofilms ofS. aureusandP. aeruginosaclinical isolates, an effect that was enhanced when they were combined as an equimolar mixture (d-Met/d-Phe/d-Trp). When combined withd-AAs, the activity of rifampin was significantly enhanced against biofilms of clinical isolates ofS. aureus, as indicated by a reduction in the minimum biofilm inhibitory concentration (MBIC) (from 32 to 8 μg/ml) and a >2-log reduction of viable biofilm bacteria compared to treatment with antibiotic alone. The addition ofd-AAs was also observed to enhance the activity of colistin and ciprofloxacin against biofilms ofP. aeruginosa, reducing the observed MBIC and the number of viable bacteria by >2 logs and 1 log at 64 and 32 μg/ml in contrast to antibiotics alone. These findings indicate that the biofilm dispersal activity ofd-AAs may represent an effective strategy, in combination with antimicrobials, to release bacteria from biofilms, subsequently enhancing antimicrobial activity.

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