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

Abstract

Metal-based antimicrobials have been used for thousands of years to treat and prevent bacterial infections. Currently, both silver and copper are used in health care and industry to prevent and treat the spread of harmful bacteria. However, like most antimicrobial agents, their efficacy against polymicrobial infections has not been fully elucidated. Coinfection with Pseudomonas aeruginosa and Staphylococcus aureus and the resulting interactions have been implicated in higher virulence, antibiotic resistance, and increased chronic infections. Here, the influence of secreted compounds from P. aeruginosa on metal antimicrobial tolerance in S. aureus was examined. This study determined that multiple compounds from P. aeruginosa increase the tolerance of S. aureus to copper and/or silver when cultured in simulated wound fluid. The presence of these secreted compounds from P. aeruginosa during exposure of S. aureus to copper or silver increased the MIC from 500 μM to 2,000 μM for copper and 16 to 63 μM for silver. The contribution of specific compounds to S. aureus tolerance was determined using gene deletion and disruption mutants, and metabolite analysis. Compounds identified as potential contributors were then individually added to S. aureus during metal exposure. Copper tolerance in S. aureus was found to be increased by amino acids and dihydroaeruginoate (Dha) secreted by P. aeruginosa. The silver tolerance provided to S. aureus was influenced only by two amino acids, serine and threonine, as well as the Pseudomonas quinolone signal (PQS) molecules from P. aeruginosa. IMPORTANCE 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.

Towards Greener Packaging: Tapioca Starch-Based Biocomposites with Siam Weed Extract and Flax Seed Gel as Sustainable Antibacterial Packaging Material

“…In the present study, the antibacterial properties of the biocomposites against the Gram-negative Staphylococcus aureus and Grampositive Pseudomonas aeruginosa were investigated. It is well known that Pseudomonas aeruginosa [30][31][32] causes severe infections in immunocompromised individuals, leading to conditions such as pneumonia, urinary tract infections, and bloodstream infections, and Staphylococcus aureus [31,33] causes infections like streptococcal infections (e.g., strep throat, scarlet fever), Clostridium difficile infections, listeriosis, enterococcal infections, diphtheria, anthrax, and tetanus. Both bacteria are capable of forming biofilms, which are slimy layers of microorganisms embedded in an extracellular matrix.…”

Copper Resistance Promotes Fitness of Methicillin-Resistant Staphylococcus aureus during Urinary Tract Infection

“…Involvement of copper resistance in the fitness of S. saprophyticus and S. epidermidis during UTI should be examined to assess if resistance to copper is a shared pathway exploited by staphylococci for survival and growth within hosts. Recently, amino acids and other effectors secreted by P. aeruginosa have been shown to protect S. aureus from copper toxicity ( 65 ). Given the common incidence of UTIs of polymicrobial etiology during catheter use, the nexus between bacterial copper resistance and fitness during UTI should also be evaluated in murine models of polymicrobial UTI.…”

Quantification of bacterial adhesion to tissue in high-throughput kinetics

“…The w.t. and Δ flg F were purchased from the Washington University Manoil laboratory mutant library [ 18 ]; the Δ pqs A and Δ las I mutants [ 19 ] were kindly provided by Professor Miguel Camara of Nottingham University; the Δ fli C and Δ pil A mutants [ 20 ] were kindly provided by Professor Martin Welch of Cambridge University. All P. aeruginosa strains tested were transformed by electroporation with the pMRP9-1 plasmid, for constitutive expression of GFPmut2 and Carbenicillin resistance [ 21 ], kindly provided by Professor Ehud Banin of the Bar Ilan University.…”