Biosynthesis of small-molecule virulence factors and development of novel antibacterials
Postdoctoral position in biosynthesis of polyketides and glycolipids in mycobacteria. The position is available to join ongoing efforts aimed at investigating the biosynthesis of bioactive polyketides and glycolipids from Mycobacterium species. Candidates must have: (i) a Ph.D. in Biochemistry; (ii) experience in protein purification and enzymology, and (iii) at least one article as first author published in an international journal. Only candidates currently in the U.S. are being considered at this time. Please send a detailed CV, including name and contact information for three references, via e-mail to: Luis Quadri, Ph.D., Associate Professor, E-mail: email@example.com.
Rationales and concepts guiding our research efforts. The numbers of global infections produced by bacterial strains that are resistant to single and multiple antimicrobial drugs are on the rise. One of the pressing goals to confront the 21st century#146;s public health challenges brought about by the escalating antibacterial drug resistance problem is the development of an armamentarium of new chemotherapeutic agents.We believe that two interconnected strategic paradigm shifts in the drug discovery process will to facilitate the achievement of this goal. One is an antimicrobial to anti-infective paradigm shift. In essence, anti infective drugs would include both drugs that render the pathogens incapable of producing infections due to antimicrobial activity (i.e., traditional antimicrobial drugs) and drugs that do so by activities other than antimicrobial. The other is a target candidate prioritization paradigm shift. This shift would contemplate moving away from a paradigm dominated by an essential target preference criterion to an alternative paradigm that relies on a less restrictive criterion, one that includes the idea that essentiality could be considered as a property that is manifested only in a particular condition or environmental context, e.g. in the human host, and would not discriminate against conditionally essential targets. By implementing this paradigm shift, bacterial functions not essential for multiplication ex vivo (e.g., on a Petri dish or culture broth), but essential for infecting the host and producing disease would not be discriminated against in the target candidate prioritization step of the drug discovery process. For example, the development of drugs that block the biosynthesis or the activity of offensive, defensive, or host environment adaptation effectors required for virulence and pathogenesis could be envisioned as the natural outcome of these paradigm shifts. These types of anti infective drugs with unconventional modes of action may be combined with classical antimicrobials to afford curative or prophylactic alternative treatment modalities. In particular, these novel anti-infectives may be useful in the fight against (multi)drug resistant strains and the prevention of their selection and dissemination (Quadri L.E.N., 2007, Strategic paradigm shifts in the antimicrobial drug discovery process of the 21st century. Infect. Disord. Drug Targets 7:230-237. Free on-line at http://www.ingentaconnect.com/content/ben/iddt/2007/00000007/00000003/art00004?token=005519fa021f12dba41333c4a2f24416a592c4046737d70253e4f6d6222346b6268763050210f28567652).
Our research efforts. Our work is primarily focused on three organisms: Mycobacterium tuberculosis (the causative agent of Tuberculosis), Yersinia pestis (the etiologic agent of Plague), and Pseudomonas aeruginosa (an opportunistic human pathogen). We apply multidisciplinary approaches to: (i) investigate the biosynthesis of non-ribosomal peptide and polyketide virulence factors, (ii) identify and characterize functions required for pathogen virulence and adaptation to the host environment, and (iii) discover and develop novel small molecules having antimicrobial activity.