Abstract

Integrative and conjugative elements (ICEs) are modular mobile genetic elements that can disseminate through excision, circularization, and transfer. Mycoplasma ICEs have recently been found distributed among some mycoplasma species and there is accumulating evidence that they play a pivotal role in horizontal gene transfers. The occurrence of ICEs has not been documented in Mycoplasma hominis, a human urogenital pathogen responsible for urogenital infections, neonatal infections and extragenital infections. In this study, we searched for, characterized, and compared ICEs by genome analyses of 12 strains of M. hominis. ICEs of 27–30 kb were found in one or two copies in seven of the 12 M. hominis strains sequenced. Only five of these ICEs seemed to be functional, as assessed by detection of circular forms of extrachromosomal ICE. Moreover, the prevalence of ICEs in M. hominis was estimated to be 45% in a collection of 120 clinical isolates of M. hominis, including 27 tetracycline-resistant tet(M)-positive isolates. The proportion of ICEs was not higher in isolates carrying the tet(M) gene, suggesting that ICEs are not involved in tetracycline resistance. Notably, all M. hominis ICEs had a very similar structure, consisting of a 4.0–5.1 kb unusual module composed of five to six juxtaposed CDSs. All the genes forming this module were specific to M. hominis ICEs as they had no homologs in other mycoplasma ICEs. In each M. hominis ICE, one to three CDSs encode proteins that share common structural features with transcription activator-like (TAL) effectors involved in polynucleotide recognition and signal transduction in symbiotic plant pathogen bacteria. The conserved and specific structure of M. hominis ICEs and the high prevalence in clinical strains suggest that these ICEs may confer a selective advantage for the physiology or pathogenicity of this human pathogenic bacterium. These data open the way for further studies aiming at unraveling horizontal gene transfers and virulence factors in M. hominis.

Highlights

  • Mycoplasma species represent a large group of wall-less bacteria derived from a common ancestor to Gram-positive bacteria, such as Clostridia (Woese et al, 1980)

  • In 2015, a comparative study including Mycoplasma ICEs (MICEs) found, in several ruminant mycoplasmas species, a conserved, minimal MICE backbone composed of four coding sequences (CDSs) predicted to be essential for MICE self-dissemination across cells (Tardy et al, 2015): CDS1, of unknown function, CDS22 encoding a DDE recombinase, and CDS5 and CDS17 encoding TraG/VirD4 and TraE/VirB4 homologs, respectively, which are predicted to be two essential components of the type IV secretion system required for DNA mobility (Citti et al, 2018)

  • We first searched for the minimal integrative and conjugative elements (ICEs) backbone composed of CDS1, CDS5, CDS17, and CDS22 using the Molligen database in the 12 fully sequenced M. hominis genomes

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Summary

Introduction

Mycoplasma species represent a large group of wall-less bacteria derived from a common ancestor to Gram-positive bacteria, such as Clostridia (Woese et al, 1980). A second MICE of 27 kb, designated as ICEA, was identified in three copies in Mycoplasma agalactiae strain 5632 (Marenda et al, 2006), a ruminant mycoplasma belonging to the same phylogenetic group Both MICEs are composed of about 20 structural genes, of which 12 are homologous. In 2015, a comparative study including MICEs found, in several ruminant mycoplasmas species, a conserved, minimal MICE backbone composed of four coding sequences (CDSs) predicted to be essential for MICE self-dissemination across cells (Tardy et al, 2015): CDS1, of unknown function, CDS22 encoding a DDE recombinase, and CDS5 and CDS17 encoding TraG/VirD4 and TraE/VirB4 homologs, respectively, which are predicted to be two essential components of the type IV secretion system required for DNA mobility (Citti et al, 2018). The detection of MICEs in several mycoplasma species of the Hominis phylogenetic group, which includes the human M. fermentans species, raised the question of whether they occur in the human M. hominis species

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