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Guerin, F.

Publications and source records attributed to Guerin, F..

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Universal trends of post-duplication evolution revealed by the genomes of 13 Paramecium species sharing an ancestral whole-genome duplication.

Whole-Genome Duplications (WGDs) have shaped the gene repertoire of many eukaryotic lineages. The redundancy created by WGDs typically results in a phase of massive gene loss. However, some WGD-derived paralogs are maintained over long evolutionary periods and the relative contributions of different selective pressures to their maintenance is still debated. Previous studies have revealed a history of three successive WGDs in the lineage of the ciliate Paramecium tetraurelia and two of its sister species from the P. aurelia complex. Here, we report the genome sequence and analysis of 10 additional P. aurelia species and one additional outgroup, allowing us to track post-WGD evolution in 13 species that share a common ancestral WGD. We found similar biases in gene retention compatible with dosage constraints playing a major role opposing post-WGD gene loss across all 13 species. Interestingly we found that post-WGD gene loss was slower in Paramecium than in other species having experienced genome duplication, suggesting that the selective pressures against post-WGD gene loss are especially strong in Paramecium. We also report a lack of recent segmental duplications in Paramecium, which we interpret as additional evidence for strong selective pressures against individual genes dosage changes. Finally, we hope that this exceptional dataset of 13 species sharing an ancestral WGD and two closely related outgroup species will be a useful resource for future studies and will help establish Paramecium as a major model organism in the study of post-WGD evolution.

evolutionary biology

Colistin heteroresistance in Enterobacter cloacae is mediated by PmrAB-independent 4-amino-4-deoxy-l-arabinose addition to lipid A

The Enterobacter cloacae complex (ECC) consists of closely-related, but genetically distinct bacteria commonly associated with the human microbiota. ECC have been increasingly isolated from healthcare-associated infections, demonstrating that these Enterobacteriaceae are emerging nosocomial pathogens. ECC strains can rapidly acquire multidrug resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the highly conserved lipid A component of the Gram-negative outer membrane to lyse the bacterial cell. Many Gram-negative Enterobacteriaceae fortify their outer membrane with cationic amine-containing moieties to protect from CAMP-inflicted lysis. The PmrAB two-component system (TCS) transcriptionally activates 4-amino-4-deoxy-O_SCPCAPLC_SCPCAP-arabinose (O_SCPCAPLC_SCPCAP-Ara4N) biosynthesis to result in amine moiety addition to lipid A in many Enterobacteriaceae such as E. coli and Salmonella. In contrast, PmrAB in E. cloacae is dispensable for CAMP resistance. Instead, fitness against CAMPs presents as heteroresistance, or a subpopulation of cells that exhibit clinically significant increases in resistance levels compared to the majority population. We demonstrate that E. cloacae lipid A is modified with O_SCPCAPLC_SCPCAP-Ara4N to induce CAMP heteroresistance and that the regulatory mechanism is independent of the PmrABEcl TCS. We show that the response regulator, PhoPEcl, directly binds to the arnBEcl promoter to induce expression of O_SCPCAPLC_SCPCAP-Ara4N biosynthesis and PmrAB-independent addition to the lipid A disaccharolipid. Therefore, we have identified a mechanism of ECC colistin heteroresistance that directly involves the PhoPQ system.\n\nImportanceMembers of the Enterobacter cloacae complex (ECC) are Gram-negative nosocomial pathogens that have emerged within healthcare facilities around the world. ECC infections are associated with immunocompromised patients and infections are often life threatening. The cationic antimicrobial peptide, colistin (polymyxin E), is a last-line treatment option to combat Gram-negative multidrug resistant infections. However, many ECC intrinsically encode a colistin heteroresistance mechanism. Our analysis to characterize colistin heteroresistance in E. cloacae revealed that 4-amino-4-deoxy-O_SCPCAPLC_SCPCAP-arabinose is conjugated to the lipid A disaccharolipid to protect from colistin-mediated lysis. Additionally, this mechanism is directly regulated by the PhoPQEcl two-component system. Elucidation of outer membrane antimicrobial resistance modifications and their regulatory pathways in E. cloacae isolates will advance our understanding of CAMP heteroresistance.

microbiology