Our Research

What do we do?

Our research involves an interdisciplinary approach using molecular genetics, biochemistry, cell biology, and structural biology to understand the pathogenesis of opportunistic Gram-negative bacteria at the molecular level. Burkholderia cenocepacia, Achromobacter species, and the Enterobacter cloacae complex are the current model organisms we use in different aspects of our research programme.

Why is it important?

Opportunistic infections pose a significant threat to human health, especially to those patients who benefit most from advancements in the treatment of genetic diseases, cancer, and organ transplantation, but who become immunosuppressed.

Burkholderia cepacia complex bacteria (Bcc) and various Achromobacter species are a potential health risk for people with cystic fibrosis and other immunocompromising conditions.

These patients commonly suffer from lung and airways infections by these microorganisms, which are very difficult to treat given the extraordinary resistance of these bacteria to clinically useful antimicrobials. Therefore, research hopes to find novel ways to prevent or ameliorate the effect of these infections in susceptible patients.

Enteric bacteria, such as Enterobacter cloacae complex isolates, are also important human pathogens highlighted by the WHO as one of the most antibiotic resistant bacteria.

In addition to our interest in understanding how all of these bacteria interact with human macrophages, we investigate the biosynthesis of lipopolysaccahride (LPS). LPS is a complex glycolipid molecule located on the surface of Gram negative bacteria that is also a critical structural component of the bacterial outer membrane. Bacteria with defects in the LPS molecule are more sensitive to various antibiotics and they can be readily killed by host defenses such as serum complement and antimicrobial peptides.

By understanding how the LPS is made, assembled on the bacterial cell surface, and modified to reduce its interactions with antimicrobial peptides we hope to design inhibitors that will interfere with this processes, which may be useful as novel antimicrobials.

Examples of key questions we currently investigate

    How opportunistic bacteria can survive the attack of antimicrobial cationic peptides and other antibiotics?
    How intracellular opportunistic bacteria delay phagosome maturation, phagosomal acidification, and the assembly of the macrophage NADPH oxidase?
    What is the role of Type 6 and Type 3 secretion systems in bacteria intracellular survival?
    How opportunisitic bacteria adapt to various environments including macrophage and epithelial cells?
    How bacterial antioxidant mechanisms protect essential bacterial metabolic pathways that are deemed to be critical for adaptation to different environments, including the lung and airways?

Sometimes genetic tools are lacking to manipulate resilient opportunistic bacteria. This is why we make efforts to developing new molecular tools and strains. For example, our lab has contributed novel tools to genetically manipulate Burkholderia, which are made available to the scientific community worldwide.


Valvano Lab Logo

Are you interested in joining our laboratory? Then read more

  • Do you enjoy adventure and exploration and don't care being frustrated from time to time?
  • Have you ever wondered how does it feel to discover something new?
  • You don't like the routine of a life without excitement
  • You would like to explore the fascinating world of microbiology but you are not a microbiologist
  • If the answer to all of the above is YES! click on any of the links below as appropriate