Berthony Deslouches
University of Pittsburgh, PA·Microbiology & Immunology
Bacteria that shrug off even last-resort drugs are a growing clinical problem, and one promising alternative is a class of short peptides that punch holes in bacterial membranes rather than attacking a single enzyme. Because they act on the membrane itself, these antimicrobial peptides can kill bacteria that already resist conventional antibiotics.
- Fields
Microbiology & Immunology
Pharmacology
Biochemistry
- Topics
antimicrobial peptides
antibiotic resistance
multidrug-resistant bacteria
- Grants
- 1 known grant, through May 2028
What they work on
- Determine how the cationic (positively charged) and hydrophobic motifs of engineered PAX peptides each contribute to recognizing and killing bacteria, by designing peptide series that vary one valine and one arginine at a time.
- Test whether PAX peptides retain potency against colistin-resistant gram-negative clinical isolates, measuring minimum inhibitory concentrations alongside red and white blood cell toxicity at maximum test concentrations.
- Generate PAX-resistant bacteria by serial passage of multidrug-resistant isolates in peptide, and identify the lipid A and LPS modifications that accompany resistance.
- Correlate peptide cationic/hydrophobic composition with LPS structural changes and bactericidal activity to build a design framework for re-engineering PAX against emerging resistance.
- Evaluate systemic efficacy and tolerated dosing of optimized PAX peptides, building on mouse infection models of multidrug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.
More about the research
But bacteria fight back: they chemically modify lipid A, the fatty, negatively charged part of the outer-membrane molecule lipopolysaccharide (LPS) that peptides latch onto, reducing its negative charge enough to blunt peptide binding. This work asks how far peptides can be redesigned to stay ahead of that defense.
Why it matters
Drug-resistant bacterial infections kill roughly 35,000 people a year in the United States, and options narrow when organisms resist colistin, a drug of last resort. Engineered cationic peptides that kill bacteria and may also neutralize bacterial endotoxin could become a treatment option for these infections. Mapping which structural features drive killing versus host toxicity, and how bacteria resist, could let peptides be re-designed as new resistance appears in patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michael Stephen Trent
University of Georgia, GA·Microbiology & Immunology
Develop an analytical tool that measures LPS molecules in transit, and combine it with mass spectrometry of the enzyme LpxC and LPS precursors to determine how the YejM-YciM system controls LPS production in E. coli.
Jason Papin
University of Virginia, VA·Biomedical Engineering
Build computational metabolic network models of antibiotic-resistant and antibiotic-sensitive Pseudomonas aeruginosa and Staphylococcus aureus in body-like environments, to predict genes and pathways that support the evolution of resistance.
Jeffrey Tornheim
Johns Hopkins University, MD·Medicine & Clinical Research
Determine how many MDR-TB patients in Mumbai carry resistance mutations that would rule out moxifloxacin, linezolid, bedaquiline, clofazimine or cycloserine, using next-generation sequencing directly from uncultured sputum.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.