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Pukatzki Lab @
The City College of
New York

What We Do

Investigations into Vibrio cholerae

We study the interactions between microbial pathogens and their hosts. To cause infections, bacteria use sophisticated strategies, some of which involve virulence factors that interact with cellular components and signaling pathways of host cells. Part of the allure of this area of research is that it not only allows us to observe a cat-and-mouse game of attack and response over evolutionary time, but it also permits us to identify novel drug targets for alternative therapies. You can read on to find out more about this exciting investigational research below.

Antibiotic Resistance

Alarming numbers of drug-resistant variants of disease-causing bacteria are emerging in an ongoing challenge to human health, because the current arsenal of antibiotics are designed to kill – thereby applying selection pressure that leads to antibiotics resistance. To develop novel therapies with reduced selection pressure and resistance emergence by disarming pathogens instead of killing them, our research focuses on understanding how pathogenic bacteria interact with their human host.

The CDC estimates that every year >two million people experience antibiotic-resistant infections in the U.S. alone, and an increasing number of patients (currently 23,000 annually) die of previously treatable infections. These alarming statistics indicate that we are returning to the pre-antibiotic era. To discover much-needed, novel targets for antimicrobials, we pioneered use of the genetically tractable amoeba Dictyostelium discoideum that identified the type VI secretion system (T6SS) as a virulence trait in the cholera bacterium Vibrio cholerae. It turns out that the T6SS is operative in almost all major Gram-negative pathogens.

Vibrio cholerae Virulence

The T6SS assembles as a molecular syringe in the bacterial envelope, allowing the bacterium to inject toxins (so-called T6SS effectors) into target cells upon contact. T6SS effectors degrade the bacterial envelope of prey bacteria, unless the prey produces immunity proteins that bind and deactivate the incoming effectors. We recently discovered that V. cholerae strains utilize distinct effectors. Strains with different effector/immunity sets compete with each other, while strains with the same effector/immunity set are compatible and co-exist when making contact. As the T6SS restricts contact between bacterial cells, we are investigating whether compatible bacteria exchange genetic (virulence) information on contact to evolve through kin selection during infection.

We aim to obtain a molecular understanding of the competitive fitness of pathogenic bacteria and its impact on virulence evolution during disease. This knowledge can be used to devise treatment strategies in which virulence is discouraged and resistant pathogens do not emerge. We view this as a chief endeavor in light of the growing multidrug resistance threat.