Clinical Implications of Polymicrobial Synergism Effects on Antimicrobial Susceptibility

Abstract

With the development of next generation sequencing technologies in recent years, it has been demonstrated that many human infectious processes, including chronic wounds, cystic fibrosis, and otitis media, are associated with a polymicrobial burden. Research has also demonstrated that polymicrobial infections tend to be associated with treatment failure and worse patient prognoses. Despite the importance of the polymicrobial nature of many infection states, the current clinical standard for determining antimicrobial susceptibility in the clinical laboratory is exclusively performed on unimicrobial suspensions. There is a growing body of research demonstrating that microorganisms in a polymicrobial environment can synergize their activities associated with a variety of outcomes, including changes to their antimicrobial susceptibility through both resistance and tolerance mechanisms. This review highlights the current body of work describing polymicrobial synergism, both inter- and intra-kingdom, impacting antimicrobial susceptibility. Given the importance of polymicrobial synergism in the clinical environment, a new system of determining antimicrobial susceptibility from polymicrobial infections may significantly impact patient treatment and outcomes.

Keywords: antimicrobial susceptibility; clinical; diagnostics; interactions; polymicrobial; synergism.

Figure 1

A schematic of two minimum inhibitory concentration (MIC) methods of antimicrobial susceptibility testing (AST) routinely used in the clinical laboratory. (A) Broth microdilution method, reprinted with permission from Heather Maughan (B) Kirby-Bauer Disk Diffusion Assay, reprinted with permission from Pearson Higher Education [2,21] (B).

Figure 2

Mechanistic bases of polymicrobial interactions. Different interactions discussed in this review are summarized here. The left column lists the types of interactions and how they are mediated with specific examples, some of which are discussed in the text. The right column demonstrates how the interaction occurs and the response of the different microbes involved and the infected host. Signals, proteins, metabolites, and even the host immune system serve as liaisons between different microbes, allowing complex interactions to occur that impact the environments in which they live. During infection, these interactions ultimately lead to polymicrobial synergy and are therefore detrimental to the host (AI-2, autoinducer-2; AHLs, acyl-homoserine lactones). Taken from [37], reprinted with permission from Journal of Microbiology (Springer Nature).