Biology subjects

Nucci, A.

Publications and source records attributed to Nucci, A..

4 recordsLinked to original sources

bioRxiv2024

Identification of novel origins of transfer across bacterial plasmids

Conjugative plasmids are important drivers of bacterial evolution, but most plasmids lack genes for conjugation. It is currently not known if the latter can transfer because origins of transfer by conjugation (oriT), which would allow their mobilization by conjugative plasmids, are poorly known. Here, we identify and characterize occurrences of known oriT families across thousands of plasmids confirming that most conjugative and mobilizable plasmids still lack identifiable families of oriTs. They reveal clear patterns in terms of intergenic position, distance to the relaxases, and MOB-type association. This allowed to develop a computational method to discover novel oriTs. As a proof of concept, we identify 21 novel oriTs from the nosocomial pathogens Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, some of them responsible for the mobility of critical antimicrobial resistance genes. These 21 oriT families share key characteristics of the others and fill most of the missing diversity of oriTs in relaxase-encoding plasmids both in terms of frequency and phylogeny. We confirmed experimentally the function of six of them. The ability to identify novel oriTs paves the way to explore conjugation across bacterial plasmids, notably among the majority lacking conjugation-related genes.

microbiology↗

bioRxiv2023

Emergence of novel non-aggregative variants under negative frequency-dependent selection in Klebsiella variicola

Klebsiella variicola is an emergent human pathogen causing diverse infections, including in the urinary tract. However, little is known about the evolution and maintenance of genetic diversity in this species, the molecular mechanisms and their population dynamics. Here, we characterized the emergence of a novel rdar-like morphotype which is contingent both on the genetic background and the environment. We show that mutations in either the nitrogen assimilation control gene (nac) or the type III fimbriae regulator, mrkH, suffice to generate rdar-like colonies. These morphotypes are primarily selected for the reduced inter-cellular aggregation as a result of loss-of-function yielding reduced fimbriae expression. Additionally, these clones also display increased growth rate and reduced biofilm formation. Direct competitions between rdar and wild type clone show that mutations in mrkH provide large fitness advantages. In artificial urine, the morphotype is under strong negative frequency-dependent selection and is able to socially exploit wild type strains. An exhaustive search for mrkH mutants in public databases revealed that ca 8% of natural isolates analysed had truncated MrkH proteins many of which were due to insertions of IS elements, including a reported clinical isolate with rdar morphology. These strains were all isolated from human, mostly from urine. The decreased aggregation of these mutants could have important clinical implications as such clones could better disperse within the host allowing colonisation of other body sites and leading to systemic infections. One-sentence SummaryReport of the emergence of a novel non-aggregative colony morphology in K. variicola and the first example of social exploitation in the Klebsiella genus.

microbiology↗

bioRxiv2023

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Bacterial evolution is affected by mobile genetic elements such as phages and conjugative plasmids, which may provide novel adaptive traits but also incur in fitness costs. Infection by these elements is affected by the bacterial capsule. Yet, its importance has been difficult to quantify and characterise because of the high diversity of bacterial genomes regarding confounding mechanisms such as anti-viral systems. We swapped capsule loci between Klebsiella pneumoniae strains to quantify their effect on transfer of conjugative plasmids and phages independently of the genetic background. Capsule swaps systematically invert phage susceptibility, demonstrating that serotypes are key determinants of phage infection. Capsule types also affect conjugation efficiency in both donor and recipient cells depending on the serotype, a mechanism shaped by the capsule volume and depending on the structure of the conjugative pilus. Comparative genomics confirmed that more permissive serotypes in the lab correspond to the strains acquiring more conjugative plasmids in nature. The pili least sensitive to capsules (F-like) are also the most frequent in the species plasmids, and are the only ones associated with both antibiotic resistance and virulence factors, driving the convergence between virulence and antibiotics resistance in the population. These results show how the traits of cellular envelopes define slow and fast lanes of infection by mobile genetic elements, with implications for population dynamics and horizontal gene transfer. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/536574v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@157bc4eorg.highwire.dtl.DTLVardef@10bc979org.highwire.dtl.DTLVardef@d85080org.highwire.dtl.DTLVardef@18d331e_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Latent evolution of biofilm formation depends on life-history and genetic background

Adaptation to one environment can often generate phenotypic and genotypic changes which impact the future ability of an organism to thrive in other environmental conditions. In the context of host-microbe interactions, biofilm formation can increase survival rates in vivo upon exposure to stresses, like the hosts immune system or antibiotic therapy. However, how the generic process of adaptation impacts the ability to form biofilm and how it may change through time has seldomly been studied. To do so, we used a previous evolution experiment with three strains of the Klebsiella pneumoniae species complex, in which we did not specifically select for biofilm formation. We observed that changes in the ability to form biofilm happened very fast at first and afterwards reverted to ancestral levels in many populations. Biofilm changes were associated to phenotypic changes in population yield and surface polysaccharide production. Genotypically, mutational targets in the tip adhesin of type III fimbriae (mrkD) or the fim switch of type I fimbriae were driven by nutrient availability during evolution, and their impact on biofilm formation was dependent on capsule production. Analyses of natural isolates revealed similar mutations in mrkD, suggesting that they also play an important role in adaptation outside the laboratory. Our work reveals that the latent evolution of biofilm formation, and its evolutionary dynamics, depend on nutrient availability, the genetic background and other intertwined phenotypic and genotypic changes. Ultimately, it suggests that small differences in the environment can alter an organisms fate in more complex niches like the host.

microbiology↗