Mycoplasmology: the big issues

Abstract

Important diseases like contagious bovine and caprine pleuropneumonia, avian mycoplasmosis, atypical pneumonia and contagious agalactia are caused by small degenerate wall-less organisms called mycoplasmas which evolved from gram positive bacteria about 2.5 billion years ago. The smallest of them are close to the theoretical limit for free-living existence containing less than 500 genes. However, they have acquired sophisticated means to survive both in the environment and in the host. Recent discoveries of their ability to survive as biofilms and within cells have changed our understanding of these degenerate bacteria. Despite increased knowledge over the last few decades, control of many mycoplasma infections seems further away than ever due to antibiotic resistance and our inability to develop effective vaccines. This review discusses some of the important issues confronting mycoplasmologists. New mycoplasmas, new diseases?It is not well known that some of the most important diseases of livestock are caused by mycoplasmas. Four are listed by the World Association for Animal Health (OIE) because of their socio-economic impacts and comprise: contagious bovine pleuropneumonia (CBPP), contagious agalactia, contagious caprine pleuropneumonia (CCPP) and avian mycoplasmosis. Others include enzootic pneumonia, a costly world-wide disease of pigs, bovine mycoplasmosis, which is characterised by respiratory disease, mastitis and arthritis, and community-acquired atypical pneumonia in humans. New outbreaks of mycoplasma disease in desert tortoises and big horn sheep have caused concern for the future of these endangered species.Mycoplasmas, or more correctly mollicutes, are the smallest self-replicating organisms on the planet and composed of wall-less, triple-layered membranes surrounding a matrix of nucleic acid and ribosomes. However once thought of as simple and possibly the precursors of more complex life they are actually highly sophisticated bacteria with elaborate defence mechanisms; in fact, they have undergone degenerative evolution from gram positive lactobacillusclostridial ancestors beginning some 2.5 billion years ago with the loss of the cell wall. Further huge gene loss occurred over the next few millennia until about 0.1 billion years the mycoplasma branch was created leading to the smallest of all mollicutes, the human pathogen Mycoplasma genitalium which consists of less than 500 genes: about a quarter of their original size and 1/10 th of the size of E. coli.The size of these organisms has generated interest in the minimum cell concept: "how many genes are essential for life?" with some estimating this figure at about 250. Attracted by this question, Craig Venter and his team in the USA attempted to put together a synthetic mycoplasma armed with the complete genome sequence of M. genitalium in the process discovering that at least 20% of the genes were not essential. After showing that they could successfully transplant genomes, they painstakingly assembled the genes of M. mycoides subsp cap...

Analysis of the immune response of calves to various saponin-based adjuvants for an experimental Mycoplasma bovis vaccine

“…Considering the divergent opinions about the role of the humoral response in preventing M. bovis infections it is suggested that the cellular immunity is likely to be more effective in eliminating M. bovis from the host than the humoral response (Nicholas et al, 2017). In this study all of the tested saponin-based adjuvants appeared to enhance the cell-mediated immune response but this depended on the adjuvant formulation.…”

“…Previously some vaccine studies have shown a stimulatory effect on humoral immunity but this was often not correlated with the prevention of M. bovis infection, disease, or colonisation of the upper and lower respiratory tract (Maunsell et al, 2009;Soehnlen et al, 2011). Considering the divergent reports it has been speculated that the cell-mediated immunity is necessary to destroy infected cells, and it is likely to be more effective in the elimination of M. bovis from the host than the humoral response (Nicholas et al, 2017). Information on the course of cellular immune response to M. bovis in young calves is limited.…”

Respiratory explants as a model to investigate early events of contagious bovine pleuropneumonia infection

“…In fact, an increasing number of mycoplasmas have been shown to enter non-phagocytic host cells [ 28 , 48 – 51 ]. The intracellular phase provides a protective niche for pathogens, in order to escape the immune defense and antimicrobial drugs [ 52 ]. Worthy of interest, we herein first demonstrated that Mmm is also able to penetrate inside non-phagocytic host cells.…”

Vpma phase variation is important for survival and persistence of Mycoplasma agalactiae in the immunocompetent host

“…Although a number of mycoplasma diseases have a huge socio-economic significance, proper control strategies are missing, mainly due to lack of knowledge about their pathogenicity mechanisms. They lack typical pathogenicity factors found in other bacteria, and although genomes of many important mycoplasma pathogens have been sequenced, questions pertaining to their virulence and survival remain [ 1 – 3 ]. Having evolved 2.5 billion years ago from a Gram-positive ancestor, mycoplasma evolution was marked by severe genomic reduction, so that contemporary mycoplasmas have lost several metabolic pathways in addition to the genes dedicated to cell wall synthesis.…”

“…agalactiae serves as an excellent model for studying mycoplasma pathogenesis because, unlike many other mycoplasma pathogens, (i) it grows well in the lab, (ii) the pathology associated with disease has been well-documented, (iii) many molecular tools, genomic and proteomic data are available, (iv) different sheep infection models are well-established, and most importantly, (v) it is phylogenetically very close to M . bovis [ 15 ], a worldwide serious pathogen that causes huge economic losses and induces similar clinical signs of mastitis, arthritis and pneumoniae in cattle [ 3 , 16 ]. Until 1976, M .…”