Unraveling Pseudomonas aeruginosa and Candida albicans Communication in Coinfection Scenarios: Insights Through Network Analysis

Abstract

Modern medicine is currently facing huge setbacks concerning infection therapeutics as microorganisms are consistently knocking down every antimicrobial wall set before them. The situation becomes more worrying when taking into account that, in both environmental and disease scenarios, microorganisms present themselves as biofilm communities that are often polymicrobial. This comprises a competitive advantage, with interactions between different species altering host responses, antimicrobial effectiveness, microbial pathogenesis and virulence, usually augmenting the severity of the infection and contributing for the recalcitrance towards conventional therapy. Pseudomonas aeruginosa and Candida albicans are two opportunistic pathogens often co-isolated from infections, mainly from mucosal tissues like the lung. Despite the billions of years of co-existence, this pair of microorganisms is a great example on how little is known about cross-kingdom interactions, particularly within the context of coinfections. Given the described scenario, this study aimed to collect, curate, and analyze all published experimental information on the molecular basis of P. aeruginosa and C. albicans interactions in biofilms, in order to shed light into key mechanisms that may affect infection prognosis, increasing this area of knowledge. Publications were optimally retrieved from PubMed and Web of Science and classified as to their relevance. Data was then systematically and manually curated, analyzed, and further reconstructed as networks. A total of 641 interactions between the two pathogens were annotated, outputting knowledge on important molecular players affecting key virulence mechanisms, such as hyphal growth, and related genes and proteins, constituting potential therapeutic targets for infections related to these bacterial-fungal consortia. Contrasting interactions were also analyzed, and quorum-sensing inhibition approaches were highlighted. All annotated data was made publicly available at , a database already containing similar data for P. aeruginosa and Staphylococcus aureus communication. This will allow researchers to cut on time and effort when studying this particular subject, facilitating the understanding of the basis of the inter-species and inter-kingdom interactions and how it can be modulated to help design alternative and more effective tailored therapies. Finally, data deposition will serve as base for future dataset integration, whose analysis will hopefully give insights into communications in more complex and varied biofilm communities.

Transcriptional response of Candida albicans to Pseudomonas aeruginosa in a polymicrobial biofilm

“… Grainha et al (2020) used previously published data to determine the interaction between C. albicans and P. aeruginosa in polymicrobial biofilms. From these data, it is evident that various different experimental approached have been taken by researchers.…”

Phloroglucinol-Gold and -Zinc Oxide Nanoparticles: Antibiofilm and Antivirulence Activities towards Pseudomonas aeruginosa PAO1

“…To date, there is no conclusive mechanism of nanoparticle biofilm inhibitory properties; however, some reports show that there is inhibition in gene expression associated with biofilm formation, altering cell membrane permeability and the production of reactive oxygen species that can disrupt cellular function [49,[54][55][56]. In addition to the formation of biofilm as an adaptive resistance mechanism, P. aeruginosa pathogenicity and chronic infection have been reported as a result of the production of an array of virulence factors involved in a variety of functions, such as motility (flagella-mediated swarming and swimming as well as type IV-pili-mediated twitching motility) and host cell damage (e.g., siderophore, protease, hemolysin, pyocyanin, exotoxin/endotoxin A, and rhamnolipid) [57]. As previously documented, quorum sensing (QS) regulates the synthesis of some virulence factors, such as hemolytic activity, pyocyanin, pyoverdine, and protease activity, of P. aeruginosa [58].…”

Bacterial Quorum-Sensing Molecules as Promising Natural Inhibitors of Candida albicans Virulence Dimorphism: An In Silico and In Vitro Study

“…Moreover, the data of virtual screening obviously demonstrated the phenomenal binding efficacy of QSMs from DKP QS system than other docked signaling systems. In contrast, a couple of earlier studies have reported the inhibitory efficacy of AHLs as well as DSFs toward C. albicans hyphal dimorphism in a dosedependent manner (Zhang et al, 2011;Grainha et al, 2020).…”

“…Following the same paradigm, certain QSMs of bacteria have been envisaged and well demonstrated to greatly influence the morphogenesis of C. albicans . For instance, the QSMs N -(3-oxododecanoyl)- l -homoserine lactone (3OC12HSL), cis -2-dodecenoic acid (BDSF), and trans -2-decenoic acid (SDSF) produced by Pseudomonas aeruginosa , Burkholderia cenocepacia , and Streptococcus mutans , respectively, have been reported to substantially limit C. albicans hyphae without altering its basic metabolism ( Grainha et al., 2020 ). Besides, it has also been deciphered that 3OC12HSL interferes with the C. albicans yeast-to-hyphal transition by mimicking the function of farnesol.…”