Other Metabolic Enzymes Functioning in Bacterial Virulence

Pyruvate Dehydrogenase Subunit B and Plasminogen Binding in Mycoplasma

Anne Grundel, Kathleen Friedrich, Melanie Pfeiffer, Enno Jacobs, and Roger Dumke

Technical University Dresden, Dresden, Germany


Species of the class Mollicutes are among the smallest self-replicating microorganisms known. The bacteria are discussed to be evolved from Gram-positive ancestors with low G/C content associated with a large reduction in their genomic resources (Citti and Blanchard 2013). The genome sizes of these cell- wall-less bacteria vary between 0.58 and 1.81 Mbp, resulting in a lack of many metabolic pathways and a limited repertoire of virulence factors in the pathogenic species among them (Kuhner et al. 2009). For instance, the tricarboxylic acid cycle and purine/pyrimidine synthesis are missing. ATP is generated mainly by glycolysis showing all reactions. Nevertheless, mycoplasmas can be found as well-adapted commensals or pathogens of plants, animals, and humans. In the latter, the organisms are successful parasites of the mucosa (urogenital or respiratory), requiring close contact with preferred host tissues. After reaching these sites by unique gliding mechanisms and adherence by specialized structures, mycoplasmas must ensure uptake of essential nutrients and escape the host's immune system. These processes are the first steps in infection and determine whether colonization will be successful or the pathogens are eliminated. The increasing number of sequenced mycoplasma genomes has resulted in deeper insights into the genomics of these microorganisms, but special tools are necessary for extensive investigations of the function of gene products (Renaudin et al. 2014). For instance, the analysis of mycoplasma metabolism and virulence is hampered by the use of a TGA codon for tryptophan and not as universal stop codon (Inamine et al. 1990), requiring effective mutation steps (Hames et al.

2005) for heterologous expression of proteins of interest.

Despite these limitations, increasing efforts have been made to improve our knowledge of the metabolic organization of mycoplasmas and to identify further factors important in the pathogenesis of infections. In this context, the interaction

Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections, First Edition. Edited by Brian Henderson.

© 2017 John Wiley & Sons, Inc. Published 2017 by John Wiley & Sons, Inc.

of bacterial proteins with host factors such as extracellular matrix (ECM) components will trigger the colonization process. In addition, the dual function of mycoplasmal proteins in metabolism and in pathogenesis is a way of compensating for the greatly reduced coding capacity of these microorganisms. Investigations in recent years have detected a number of surface-exposed proteins in mycoplasma that function as so-called microbial surface components, recognizing adhesive matrix molecules (MSCRAMMs). These include toxins and cytadhesins which play a primary role as virulence factors (Hopfe and Henrich 2014). Furthermore, glycolytic enzymes with moonlighting functions have been found in various species (Table 18.1). Among them are proteins that interact with different host components as well as particular host proteins that bind to different glycolytic enzymes, suggesting a network of associations between host and mycoplasma factors. Investigation of these associations in more comprehensive studies appears promising in terms of gaining an overall insight into the importance of glycolytic enzymes as surface-displayed proteins.

Due to its importance for public health, M. pneumoniae is one of the best investigated among mycoplasma species. M. pneumoniae is a common agent in a broad range of human respiratory tract infections ranging from mild forms of tracheobronchitis to severe cases of atypical pneumonia requiring hospitalization of patients (Atkinson et al. 2008). In epidemic periods, which occur every three to seven years, up to 30% of all cases of community-acquired pneumonia can be attributed to this pathogen (Dumke et al. 2015). In addition, extra-pulmonary manifestations are described, affecting mainly the skin and the central nervous system. Knowledge of further details of the infection and colonization process is key to understanding the particular epidemiology of diseases due to these bacteria. Research activities in the past have focused on virulence factors such as the tip structure in M. pneumoniae (Hasselbring et al. 2006). This attachment organelle comprises a complex of adhesins and adhesion-related proteins, which targets the cells of the respiratory epithelium.

Table 18.1 Described glycolytic enzymes with multifunction in Mycoplasma/Spiroplasma.


Host interaction Glycolytic enzyme partner


M. bovis



Song et al. (2012)

M. fermentans



Yavlovich et al. (2007)

M. gallisepticum



Chen et al. (2011)

M. genitalium



Alvarez et al. (2003)

M. pneumoniae



Dumke et al. (2011)



Dallo et al. (2002)


Thomas et al. (2013)



Thomas et al. (2013)

M. suis



Schreiner et al. (2012)



Hoelzle et al. (2007)

M. synoviae



Bao et al. (2014)


S. citri



Labroussaa et al. (2011)

* Phosphoglycerate kinase.

Subsequently, the expression of tissue-damaging substances such as superoxide (Hames et al. 2009) and the CARDS toxin (Kannan and Baseman 2006) have been described as important aspects of successful host colonization.

For investigation of proteins with multiple functions in bacteria, species such as M. pneumoniae are the simplest models for studying the role of these proteins in host-pathogen interactions. With 693 proposed protein-coding genes and descriptions of the function of about 70% of protein-coding genes, M. pneumoniae is a promising candidate for studying the complete proteome of a bacterium (Catrein and Herrmann 2011). Previous proteomic analysis revealed a number of glycolytic enzymes occurring in the fraction of membrane-associated proteins extracted after treatment of M. pneumoniae cells with the detergent Triton X-100 (Regula et al. 2001). Among these, the subunits A and B of pyruvate dehydrogenase (PDH) were found to belong to the PDH complex (Matic et al. 2003). During glycolysis, the enzymes of the complex convert pyruvate to acetyl-CoA. The cluster in M. pneumoniae consists of four genes pdhA to D transcribed in this order (Dandekar et al. 2000) and is intermitted by the small MP200 RNA (Gohlmann et al. 2000). The subunits of the PDH cluster are phosphorylated like many enzymes in glycolysis (Schmidl et al. 2010), allowing regulation of their activity and localization. Furthermore, subunit A (E1 a) of PDH was described as complexed to the major P1 adhesin (Layh-Schmitt et al. 2000), indicating that an interaction of this class of proteins with the adherence apparatus of M. pneumoniae cannot be excluded.

< Prev   CONTENTS   Source   Next >