Microbes display a remarkable ability to adapt to a huge range of environments. In the Spero Lab, we study how bacteria behave in host environments, and in turn, how those behaviors impact human health.
Our work currently focuses on how bacteria behave during chronic infections. Chronic infections can persist for months to decades despite aggressive antibiotic therapy. Antibiotic treatment failure is often not due to antibiotic resistance. We posit that the chemical and physical landscape of the host environment leads bacteria to become less metabolically active and to form biofilms, two phenotypes that are linked to antibiotic treatment failure.
The questions that guide our research include:
• What environmental parameters do bacteria encounter within the host?
• What processes do bacteria rely on for long-term survival in the host?
• What regulates bacterial biofilm formation?
• What environmental conditions promote antibiotic-tolerant states in different organisms?
• Can we leverage our understanding of bacterial physiology to design more effective treatments for combatting chronic infections?
We investigate these questions in different chronic infection-associated pathogens, including Pseudomonas aeruginosa, and the obligate anaerobic bacteria, Finegoldia magna and Anaerococcus vaginalis.
Some interesting findings:
P. aeruginosa becomes highly tolerant to the antibiotic tobramycin under anoxic, slow-growth conditions. Importantly, chronic infection environments are often oxygen-limited.
(Spero & Newman. 2018. mBio)
P. aeruginosa requires anaerobic nitrate respiration to perpetuate chronic wound infections.
(Kim, Spero, et al. 2023. Adv Wound Care)
Chlorate is a small molecule that is toxic to bacteria when they use anaerobic nitrate respiration. Chlorate kills hypoxic populations of P. aeruginosa biofilms, which are tolerant to antibiotics like tobramycin. These findings demonstrate that we can leverage our understanding of bacterial physiology in host environments to develop new therapeutic strategies that overcome antibiotic treatment failure.
(Spero & Newman. 2018. mBio)
Biofilms are notoriously hard to kill with antibiotics. We aim to understand what regulates biofilm formation across different bacteria. Finegoldia magna exhibits diverse biofilm phenotypes in different growth media.
