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International audience; Antibiotics are majorly important molecules for human health. Following the golden age of antibiotic discovery, a period of decline ensued, characterised by the rediscovery of the same molecules. At the same time, new culture techniques and high-throughput sequencing enabled the discovery of new microorganisms that represent a potential source of interesting new antimicrobial substances to explore. The aim of this review is to present recently discovered nonribosomal peptide (NRP) and polyketide (PK) molecules with antimicrobial activity against human pathogens. We highlight the different in silico/in vitro strategies and approaches that led to their discovery. As a result of technological progress and a better understanding of the NRP and PK synthesis mechanisms, these new antibiotic compounds provide an additional option in human medical treatment and a potential way out of the impasse of antibiotic resistance.

International audience; Living organisms interact with each other during their lifetime, leading to genomes rearrangement and sequences transfer. These well-known phenomena give these organisms mosaic genomes, which challenge their classification. Moreover, many findings occurred between the IXXth and XXIst century, especially the discovery of giant viruses and candidate phyla radiation (CPR). Here, we tried to provide an updated classification, which integrates 216 representative genomes of the current described organisms. The reclassification was expressed through a genetic network based on the total genomic content, not on a single gene to represent the tree of life. This rhizomal exploration represents, more accurately, the evolutionary relationships among the studied species. Our analyses show a separated branch named fifth TRUC (Things Resisting Uncompleted Classifications). This taxon groups CPRs together, independently from Bacteria, Archaea (which regrouped also Nanoarchaeota and Asgard members), Eukarya, and the giant viruses (recognized recently as fourth TRUC). Finally, the broadening of analysis methods will lead to the discovery of new organisms, which justify the importance of updating the classification at every opportunity. In this perspective, our pragmatic representation could be adjusted along with the progress of evolutionary studies.

International audience; ABSTRACT Fosfomycin is a decades-old antibiotic, currently reused because of its activity against multidrug-resistant bacteria. Here, we used a combined in vitro/in silico approach to search for fosfomycin resistance determinants in 25 new bacterial species isolated from the human microbiota. Putative resistance genes were cloned into a susceptible Escherichia coli strain. MIC values increased from 1 μg/ml to 1,024 μg/ml. Here, we report a new family of potential chromosomal fosfomycin resistance genes, named fosM .

International audience; Genome remodeling and exchange of sequences are widespread in the prokaryotic world and mosaic genomes challenge the classification of prokaryotes, which cannot be properly achieved in terms of a single gene or group of genes. Here, we studied individually the gene collection of the archaic microorganism Lokiarchaeum sp., suggested as an archaeal host close to the emergence of the eukaryotes. The network or rhizome of all Lokiarchaeum sp. genes revealed that the genomic repertoire is mainly composed of genes from archaeal (similar to 36%) and bacterial origin (similar to 28%), distantly followed by components of eukaryotic origin (similar to 2%). Thirty-three percent of genes were unique to this species (ORFans). The mosaicity of archaea was also supported by studying Methanomassiliicoccus luminyensis, an archaea from the gut, in which 67% of the genomic repertoire arised from archaea and 22% from bacteria. Our results illustrate the intricate evolutionary relationships of the archaeal genome repertoire and highlight the rhizome-like processes of evolution in archaea, their mosaicity, and chimeric origin composed of different domains of life, questioning the reality of a tree of life.

International audience; Obesity represents a worldwide public health crisis. Trials suggested that intestinal microbiota may contribute to the development of obesity and highlighted the involvement of bacteria, including Lactobacillus spp., in changes to the host metabolism. Several experiments have shown significant effects of Lactobacillus probiotics on weight modification. Lactobacillus spp. are involved in the digestion of complex carbohydrates not digested by the host in the colon and also participate in the degradation of lipids and simple sugars in the duodenum and jejunum. Moreover, Lactobacillus species survive throughout the gastrointestinal tract, as they are able to survive in the presence of bile and low pH, and produce an antimicrobial agent, allowing them to reduce the number of bacteria in the gut. Hence, Lactobacillus spp. can have a significant impact on microbiota and, consequently, on weight change. Here, we review current studies of Lactobacillus spp. involved in weight change and discuss the different mechanisms of action by which Lactobacillus spp. acts on host digestion and appears to influence weight. Published by Elsevier Ltd.

International audience; The history of infectious diseases raised the plague as one of the most devastating for human beings. Far too often considered an ancient disease, the frequent resurgence of the plague has led to consider it as a reemerging disease in Madagascar, Algeria, Libya, and Congo. The genetic factors associated with the pathogenicity of Yersinia pestis, the causative agent of the plague, involve the acquisition of the pPCP1 plasmid that promotes host invasion through the expression of the virulence factor Pla. The surveillance of plague foci after the 2003 outbreak in Algeria resulted in a positive detection of the specific pla gene of Y. pestis in rodents. However, the phenotypic characterization of the isolate identified a Citrobacter koseri. The comparative genomics of our sequenced C. koseri URMITE genome revealed a mosaic gene structure resulting from the lifestyle of our isolate and provided evidence for gene exchanges with different enteric bacteria. The most striking was the acquisition of a continuous 2 kb genomic fragment containing the virulence factor Pla of the Y. pestis pPCP1 plasmid; however, the subcutaneous injection of the CKU strain in mice did not produce any pathogenic effect. Our findings demonstrate that fast molecular detection of plague using solely the pla gene is unsuitable and should rather require Y. pestis gene marker combinations. We also suggest that the evolutionary force that might govern the expression of pathogenicity can occur through the acquisition of virulence genes but could also require the loss or the inactivation of resident genes such as antivirulence genes.

Background Rickettsia prowazekii is the etiological agent of epidemic typhus and is an obligate intracellular bacterium that grows as a parasite freely within the cytoplasm of a eukaryotic host cell. Previous studies have shown that rOmpA and rOmpB which belong to the family of rickettsial cell surface antigens are involved in vitro in the adhesion of Rickettsiae to epithelial cells. Recently, two putative rickettsial adhesins have been identified using high resolution 2D-PAGE coupled with mass spectrometry. In this study, we further characterize and describe the adhesin Adr2 from R. prowazekii . Methodology/Principal findings Using an overlay assay coupled with mass spectrometry two adhesins, Adr1 (RP827) and Adr2 (RP828), were identified from the R. prowazekii proteome Recombinant R. prowazekii Adr2 was expressed through fusion with Dsbc in Escherichia coli , purified and concentrated, thus allowing production of specific monoclonal antibodies, as confirmed by western blot assays. Finally, inhibition of rickettsiae-induced cytotoxicity with monoclonal anti-Adr2 antibody has showed a greatest impact on bacterial cell entry at 8 h post-infection (ca50%) and then decreased progressively to attempt 18% of inhibition at day 7. These, correlated to the inhibition of rickettsiae-induced cytotoxicity with monoclonal anti-rOmpB antibody. Thus, Adr2 is sufficient to mediate R. prowazekii entry into the cell at early stage of mammalian cell infection. Conclusions Our results suggest that R. prowazekii Adr2 could be the main actor promoting the entry of rickettsiae into the host cells. The present study opens the framework for future investigations for better understanding of the Adr2 -mediated mechanisms involved in adhesion/invasion or intracellular survival of R. prowazekii .

International audience; The intracellular flea symbiont, Rickettsia felis, may meet other organisms intracellularly such as R. typhi. We used a single-gene phylogenetic approach of the 1375 R. felis genes to look for horizontal transfers that occurred as a result of the bacterial promiscuity with other organisms. Our results showed that besides genes that are linked to the Spotted Fever Group, 165 genes have a different history and are linked to other Rickettsia such as R. bellii (107 genes), R. typhi (15 genes), or to other bacteria such as Legionella sp. and Francisella sp. or to eukaryotes. Among these genes, we identified 73 individual genes and 34 spatial clusters containing 2–4 adjacent genes, a total of 79 genes, with evidence of en bloc transfer. We described 13 chimeric genes resulting from gene recombination with sympatric R. typhi. The transferred DNA sequences present different sizes and functions, suggesting that the horizontal transfer in R. felis is random and neutral within its specific host. Our study shows that the strict intracellular bacteria R. felis exhibits a mosaic genome. We therefore developed a new representation for the evolutionary history of R. felis showing its different putative ancestors in the form of a rhizome.

Background Genome size and gene content in bacteria are associated with their lifestyles. Obligate intracellular bacteria (i.e., mutualists and parasites) have small genomes that derived from larger free-living bacterial ancestors; however, the different steps of bacterial specialization from free-living to intracellular lifestyle have not been studied comprehensively. The growing number of available sequenced genomes makes it possible to perform a statistical comparative analysis of 317 genomes from bacteria with different lifestyles. Results Compared to free-living bacteria, host-dependent bacteria exhibit fewer rRNA genes, more split rRNA operons and fewer transcriptional regulators, linked to slower growth rates. We found a function-dependent and non-random loss of the same 100 orthologous genes in all obligate intracellular bacteria. Thus, we showed that obligate intracellular bacteria from different phyla are converging according to their lifestyle. Their specialization is an irreversible phenomenon characterized by translation modification and massive gene loss, including the loss of transcriptional regulators. Although both mutualists and parasites converge by genome reduction, these obligate intracellular bacteria have lost distinct sets of genes in the context of their specific host associations: mutualists have significantly more genes that enable nutrient provisioning whereas parasites have genes that encode Types II, IV, and VI secretion pathways. Conclusion Our findings suggest that gene loss, rather than acquisition of virulence factors, has been a driving force in the adaptation of parasites to eukaryotic cells. This comparative genomic analysis helps to explore the strategies by which obligate intracellular genomes specialize to particular host-associations and contributes to advance our knowledge about the mechanisms of bacterial evolution. Reviewers This article was reviewed by Eugene V. Koonin, Nicolas Galtier, and Jeremy Selengut.