Using Informatics and Molecular Biology to Understand Chronic Bacterial Infection Physiology

Chronic bacterial infections pose a significant global health challenge, leading to considerable health and economic consequences. These bacteria can evade the host’s immune response and resist multi-drug therapies, enabling survival for long periods in the body. Despite extensive research, the specific mechanisms underlying chronic infection symptomatic and asymptomatic phases remain poorly understood.

The Ross lab uses Mycobacterium abscessus (MAB) as a model system due to its ability to alter colony morphotypes in real time during infection. The smooth form of this bacteria might not cause noticeable symptoms, but when it changes to a rough form, it can lead to increased inflammation and more severe symptomatic illness in patients. By employing libraries of gene mutants, we have identified distinct differences in gene requirements both in vitro and during infection, shedding light on why the different forms of M. abscessus have varying impacts on pathology.

Our lab has several graduate projects to choose from that explore:

1. why some genes are crucial for either symptomatic or asymptomatic infections of M. abscessus,
2. what factors during infection determine the importance of these genes, and,
3. whether targeting specific genes can help manage infection outcomes, especially inflammation and tissue damage.

We have expertise in bioinformatics, molecular biology, CRISPRi, confocal microscopy, and infection modeling, which we will be leveraged to address these questions.

The driving force behind our research is the growing problem of antibiotic resistance. Chronic infections not only contribute to the emergence of new resistant strains but also feature asymptomatic phases. By manipulating bacterial physiology between these states, we aim to enhance bacterial clearance or maintain an asymptomatic condition, thereby providing patients with critical time when antibiotics are unavailable.