Biology subjects

Hsieh, Y.-Y. P.

Publications and source records attributed to Hsieh, Y.-Y. P..

3 recordsLinked to original sources

bioRxiv2024

A novel PhoPQ-potentiated mechanism of colistin resistance impairs membrane integrity in Pseudomonas aeruginosa

Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. We previously reported that magnesium sequestration by Candida albicans enables Pseudomonas aeruginosa to become colistin-resistant. Here, we show that Mg{superscript 2} depletion drives P. aeruginosa to evolve greater colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway relies on early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced binding of colistin to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity unleashes two novel trajectories of colistin resistance evolution in P. aeruginosa. (160)

microbiology↗

bioRxiv2023

Widespread fungal-bacterial competition for magnesium enhances antibiotic resistance

Fungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Using unbiased genomic approaches, we discover that the fungus Candida albicans sequesters essential Mg2+ ions from the bacterium Pseudomonas aeruginosa. In turn, the bacterium competes using a Mg2+ transporter, MgtA. We show that Mg2+ sequestration by fungi is a general mechanism of antagonism against gram-negative bacteria. But the resultant Mg2+ limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Experimental evolution reveals that bacteria in co-culture with fungi become phenotypically, but not genetically, resistant to colistin; antifungal treatment renders resistant bacteria from co-cultures to become colistin-sensitive. Fungal-bacterial nutritional competition may thus profoundly impact treatments of polymicrobial infections with antibiotics of last resort. One Sentence SummaryMagnesium sequestration by fungi lowers bacterial fitness but enhances antibiotic resistance.

microbiology↗

bioRxiv2019

Evolutionary repair: changes in multiple functional modules allow meiotic cohesin to support mitosis

Different members of the same protein family often perform distinct cellular functions. How much are these differing functions due to changes in a proteins biochemical activity versus changes in other proteins? We asked how the budding yeast, Saccharomyces cerevisiae, evolves when forced to use the meiosis-specific kleisin, Rec8, instead of the mitotic kleisin, Scc1, during the mitotic cell cycle. This perturbation impairs sister chromosome linkage and reduces reproductive fitness by 45%. We evolved 15 populations for 1750 generations, substantially increasing their fitness, and analyzed their genotypes and phenotypes. We found no mutations in Rec8, but many populations had mutations in the transcriptional mediator complex, cohesin-related genes, and cell cycle regulators that induce S phase. These mutations improve sister chromosome cohesion and slow genome replication in Rec8-expressing cells. We conclude that changes in known and novel partners allow proteins to improve their ability to perform new functions.

evolutionary biology↗