Biology subjects

Alzheimer, M.

Publications and source records attributed to Alzheimer, M..

4 recordsLinked to original sources

bioRxiv2026

Interdependent mode of RNA recognition by the interacting KH-domain proteins KhpA and KhpB

RNA-binding proteins (RBPs) are central regulators of gene expression. In bacteria, two KH domain-containing proteins, KhpA and KhpB, are increasingly recognized as globally-acting RBPs, including in pathogens that lack well-studied RBPs, such as Hfq and ProQ. While KhpA and KhpB interact with various RNAs in diverse bacteria, their crosstalk and molecular basis of RNA recognition remain poorly understood. Here, we explored the mutual dependence between KhpA and KhpB in the food-borne pathogen Campylobacter jejuni. We demonstrate KhpA and KhpB interact in vivo, and their individual global RNA recognition is largely dependent on the presence of the partner protein. Using RNA co-immunoprecipitation, we reveal that KhpA requires a conserved KH domain motif for RNA binding, whereas KhpB relies on an atypical R3H domain. Moreover, mutating the RNA-binding domain of one protein compromises the RNA interactome of the other. Overall, we demonstrate an interdependent RNA-binding mode of KhpA and KhpB and anticipate that such KH-proteins have co-evolved to elicit joint RNA regulation in bacteria.

microbiology↗

bioRxiv2026

Human-targeted drugs impact antibiotic sensitivity and growth of Campylobacter jejuni

Antibiotic resistance is increasingly recognized as a major threat to global health, yet the contribution of non-antibiotics to this problem remains poorly defined. Here, we established a transcriptional chemical genomics approach to map how 2,415 host-relevant small molecules influence stress-responsive promoters and fitness of the foodborne pathogen Campylobacter jejuni. This screen uncovered widespread activation of the CmeABC efflux pump by diverse compounds, including several human-targeted drugs. Notably, ibuprofen, one of the most widely used non-steroidal anti-inflammatory drugs worldwide, induced efflux pump expression and thereby enhanced bacterial tolerance to ciprofloxacin. We also identified multiple commensal-sparing human-targeted drugs with growth-inhibitory activity against C. jejuni, highlighting opportunities for pathogen-targeted drug repurposing. Together, our findings reveal that non-antibiotic drugs can both promote resistance-associated phenotypes and selectively suppress pathogen growth. This underscores the need to consider collateral drug effects on bacterial physiology when designing strategies to curb the burden of antimicrobial resistance.

microbiology↗

bioRxiv2025

Functional genomics of Campylobacter-host interactions in an intestinal tissue model reveals a small lipoprotein essential for flagellar assembly

Campylobacter jejuni is the leading cause of bacterial food-poisoning, with motility being an essential virulence factor. While many aspects of flagella biogenesis have been studied, a complete picture of the components and regulators of these multi-protein machines is still missing. To identify genes crucial for C. jejuni pathogenesis and motility, we applied transposon sequencing in a humanized tissue model. This revealed three largely uncharacterized genes (pflC , pflD , pflE ) as essential for motility. While PflC/D turned out to be components of the flagellar motor disk structures, PflE is a small protein of only 57 aa. PflE strikingly affects motor biogenesis, with complete loss of motor structures upon its deletion. We demonstrate PflE is a lipoprotein and supports outer-membrane localization of the main basal-disk protein FlgP. With motility as a critical Campylobacter virulence factor, our work demonstrates that deletion of a small protein can bring a bacterial pathogen to a halt.

microbiology↗

bioRxiv2023

Molecular model of a bacterial flagellar motor in situ reveals a "parts-list" of protein adaptations to increase torque

One hurdle to understanding how molecular machines work, and how they evolve, is our inability to see their structures in situ. Here we describe a minicell system that enables in situ cryogenic electron microscopy imaging and single particle analysis to investigate the structure of an iconic molecular machine, the bacterial flagellar motor, which spins a helical propeller for propulsion. We determine the structure of the high-torque Campylobacter jejuni motor in situ, including the subnanometre-resolution structure of the periplasmic scaffold, an adaptation essential to high torque. Our structure enables identification of new proteins, and interpretation with molecular models highlights origins of new components, reveals modifications of the conserved motor core, and explain how these structures both template a wider ring of motor proteins, and buttress the motor during swimming reversals. We also acquire insights into universal principles of flagellar torque generation. This approach is broadly applicable to other membrane-residing bacterial molecular machines complexes.

molecular biology↗