Evidence for bacterial co-infections is increasing
Image credit: Deborah Yung (and check out more of her designs here: @Debz_microart)
In complex infectious diseases the invading microorganisms are often polymicrobial (multiple infectious agents) and very little is known about the impact of these microbial communities in the progression of the infection that causes significant morbidity and mortality. Bacterial co-infections can also lead to increased antimicrobial resistance and antibiotic tolerance.
As model organisms to study polymicrobial infections, we use the two opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus, both are most commonly co-isolated from chronic wounds and the sputum of cystic fibrosis patients. Over the last few years, there have been plenty of contrasting results from studies involving P. aeruginosa and S. aureus co-cultures. Our research explores this complicated relationship with strains that either co-exist or harm each other.
Polymicrobial infection models to study drug efficacy
A detailed understanding of the mechanisms of complex polymicrobial infections are still lacking. Therefore, we strive to shed light on these biological processes by studying polymicrobial communities in vitro and polymicrobial skin and lung infections in vivo.
We have developed a Pseudomonas–Staphylococcus co-culture biofilm model in host-mimicking conditions and in a novel murine cutaneous abscess model that allows us to study their interaction and changes in susceptibility to antibiotics and new drug compounds.
On the other hand, to study the antagonist behaviour of those two pathogens, we utilize transposon mutants to investigate the molecular players involved in killing mechanisms of each other.
Expanding from these two model organisms, we also investigate co-cultures of common human skin and lung pathogens including Staphylococcus, Enterococcus, and Cutibacterium as well Klebsiella and Acinetobacter.
How do polymicrobial infections alter the immune response?
We also explore important questions such as how microbial interaction influences immune responses, how multiple microbes contribute to disease progression, and how to effectively treat infectious diseases.
We use a two-pronged approach, investigating how pathogenic traits of one bacterium might be altered either through direct bacterial interaction of the other bacterium or indirectly through the activation and modulation of alternative host responses. In addition, we study how polymicrobial colonization and exposure leads to the induction of different host immune response pathways to determine how this influences disease progression.
Further reading ...
Yung DBY, Sircombe KJ, Pletzer D. Friends or enemies? The complicated relationship between Pseudomonas aeruginosa and Staphylococcus aureus. Mol Microbiol. 2021 Jul;116(1):1-15. doi: 10.1111/mmi.14699.
Alford MA, Choi KG, Trimble MJ, Masoudi H, Kalsi P, Pletzer D, Hancock REW. Murine Model of Sinusitis Infection for Screening Antimicrobial and Immunomodulatory Therapies. Front Cell Infect Microbiol. 2021 Mar 12;11:621081. doi: 10.3389/fcimb.2021.621081.
Wu BC, Haney EF, Akhoundsadegh N, Pletzer D, Trimble MJ, Adriaans AE, Nibbering PH, Hancock REW. Human organoid biofilm model for assessing antibiofilm activity of novel agents. NPJ Biofilms Microbiomes. 2021 Jan 25;7(1):8. doi: 10.1038/s41522-020-00182-4.
Coleman SR, Pletzer D, Hancock REW. Contribution of Swarming Motility to Dissemination in a Pseudomonas aeruginosa Murine Skin Abscess Infection Model. J Infect Dis. 2021 Aug 16;224(4):726-733. doi: 10.1093/infdis/jiaa778.
Belanger CR, Lee AH, Pletzer D, Dhillon BK, Falsafi R, Hancock REW. Identification of novel targets of azithromycin activity against Pseudomonas aeruginosa grown in physiologically relevant media. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33519-33529. doi: 10.1073/pnas.2007626117.
Khomtchouk KM, Kouhi A, Xia A, Bekale LA, Massa SM, Sweere JM, Pletzer D, Hancock RE, Bollyky PL, Santa Maria PL. A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation. Sci Adv. 2020 Aug 14;6(33):eabc1828. doi: 10.1126/sciadv.abc1828.
Belanger CR, Mansour SC, Pletzer D, Hancock REW. Alternative strategies for the study and treatment of clinical bacterial biofilms. Emerg Top Life Sci. 2017 Apr 21;1(1):41-53. doi: 10.1042/ETLS20160020.