In press @ Nature Comm. “Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization”

Tory’s paper in press @ Nature Comm. “Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization”. Her paper reports a new mechanism that gives rise to antibiotic synergy. Download the full pre-print version: https://escholarship.org/uc/item/4vd662tn.

First proposed as antimicrobial agents, histones were later recognized for their role in condensing chromosomes. Histone antimicrobial activity has been reported in innate immune responses. However, how histones kill bacteria has remained elusive. The co-localization of histones with antimicrobial peptides (AMPs) in immune cells suggests that histones may be part of a larger antimicrobial mechanism in vivo. Here we report that histone H2A enters E. coli and S. aureus through membrane pores formed by the AMPs LL-37 and magainin-2. H2A enhances AMP-induced pores, depolarizes the bacterial membrane potential, and impairs membrane recovery. Inside the cytoplasm, H2A reorganizes bacterial chromosomal DNA and inhibits global transcription. Whereas bacteria recover from the pore-forming effects of LL-37, the concomitant effects of H2A and LL-37 are irrecoverable. Their combination constitutes a positive feedback loop that exponentially amplifies their antimicrobial activities, causing antimicrobial synergy. More generally, treatment with H2A and the pore-forming antibiotic polymyxin B completely eradicates bacterial growth.

KEYWORDS: Mammalian histones, neutrophil extracellular traps, lipid droplets, bacterial chromosomal organization, antimicrobial synergy, host-microbe, proton gradient

Calvin, Frank, and Jennifer graduate

Congratulations to the class of 2020. Calvin Trinh, Frank Ramirez, and Jennifer Poo are graduating. Calvin and Jennifer will be working towards …

Louis’ paper in press @ JoVE: Time-lapse Imaging of Bacterial Swarms and the Collective Stress Response

https://www.jove.com/video/60915/time-lapse-imaging-bacterial-swarms-collective-stress

Summary: We detail a simple method to produce high-resolution time-lapse movies of Pseudomonas aeruginosa swarms that respond to bacteriophage (phage) and antibiotic stress using a flatbed document scanner. This procedure is a fast and simple method for monitoring swarming dynamics and may be adapted to study the motility and growth of other bacterial species

Now @mBio: Kumar’s paper on metabolic dynamics in bacterial biofilms

https://mbio.asm.org/content/11/2/e02730-18.abstract

The rise of antibiotic resistance requires the development of new strategies to combat bacterial infection and pathogenesis. A major direction has been the development of drugs that broadly target virulence. However, few targets have been identified due to the species-specific nature of many virulence regulators. The lack of a virulence regulator that is conserved across species has presented a further challenge to the development of therapeutics. Here, we identify that NADH activity has an important role in the induction of virulence in the pathogen P. aeruginosa. This finding, coupled with the ubiquity of NADH in bacterial pathogens, opens up the possibility of targeting enzymes that process NADH as a potential broad antivirulence approach.