The mechanisms underlying antigenic variation and maintenance of genomic integrity in Mycoplasma pneumoniae and Mycoplas

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The mechanisms underlying antigenic variation and maintenance of genomic integrity in Mycoplasma pneumoniae and Mycoplasma genitalium Mohamad S. Hakim1,2   · Luthvia Annisa1 · Rizka O. A. Jariah3 · Cornelis Vink4 Received: 28 May 2020 / Revised: 2 August 2020 / Accepted: 12 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Mycoplasma pneumoniae and Mycoplasma genitalium are important causative agents of infections in humans. Like all other mycoplasmas, these species possess genomes that are significantly smaller than that of other prokaryotes. Moreover, both organisms possess an exceptionally compact set of DNA recombination and repair-associated genes. These genes, however, are sufficient to generate antigenic variation by means of homologous recombination between specific repetitive genomic elements. At the same time, these mycoplasmas have likely evolved strategies to maintain the stability and integrity of their ‘minimal’ genomes. Previous studies have indicated that there are considerable differences between mycoplasmas and other bacteria in the composition of their DNA recombination and repair machinery. However, the complete repertoire of activities executed by the putative recombination and repair enzymes encoded by Mycoplasma species is not yet fully understood. In this paper, we review the current knowledge on the proteins that likely form part of the DNA repair and recombination pathways of two of the most clinically relevant Mycoplasma species, M. pneumoniae and M. genitalium. The characterization of these proteins will help to define the minimal enzymatic requirements for creating bacterial genetic diversity (antigenic variation) on the one hand, while maintaining genomic integrity on the other. Keywords  Antigenic variation · DNA repair · Homologous DNA recombination · M. genitalium · M. pneumoniae

Introduction

Communicated by Michael Berney. * Mohamad S. Hakim [email protected] * Cornelis Vink [email protected] 1



Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, 55281 Yogyakarta, Indonesia

2



Postgraduate School of Molecular Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands

3

Department of Health Science, Faculty of Vocational Studies, Universitas Airlangga, Surabaya, Indonesia

4

Department of Life Sciences, Erasmus University College, Erasmus University, 3011 HP Rotterdam, The Netherlands



Mycoplasma pneumoniae and Mycoplasma genitalium are pathogenic bacteria that cause significant health problems in the human population. These pathogens are genetically very similar (Himmelreich et al. 1997), and belong to the Mollicutes class of bacteria. While the genome of M. pneumoniae is significantly longer than that of M. genitalium (816 kb versus 580 kb) (Fraser et al. 1995; Himmelreich et al. 1996), the ~ 479 orthologous proteins encoded by these species on average display ~ 67% identity (Himmelreich et al. 1997). M. pneumoniae causes both upper respiratory