Clostridium difficile: A bad bug goes into defensive mode

Clostridium difficile was first isolated in 1935 from the stool sample of a healthy infant and was originally described as Bacillus difficilus (Hall and O’Toole, 1935). The difficulties experienced during the isolation and maintenance of this microorganism in the laboratory stuck with its name when it was re-classified as a member of the genus Clostridium. Recent taxonomic considerations that are based upon an expanded 16S gene sequence hierarchical framework (Collins et al., 1994) lead to its further re-classification as Clostridioides difficile (Lawson et al., 2016). This name was chosen to reflect (i) its similarity to Clostridium (Clostridioides 5 organisms similar to Clostridium) but (ii) without causing wide-ranging ramifications that would ensue when the use of the well-established abbreviations (C. difficile, or C. diff) for its name would no longer be possible in commercial and clinical setting (Lawson et al., 2016). This will happen if the proposal to taxonomically affiliate C. difficile with the genus Peptoclostridium is followed (Yutin and Galperin, 2013). Leaving taxonomic considerations and controversies aside, C. difficile is a rising star among unsavory microorganisms, causing hundreds of thousands of infections and thousands of deaths and burdening European and North American health care systems with billions of dollars for its treatment. About half a million cases of infections with C. difficile are estimated for the United States alone for the year 2011, leading to about 29 000 deaths and costs of 4.8 billion dollars for acute care facilities (Lessa et al., 2015). This dire situation is acerbated by the appearance of hyper-virulent variants of C. difficile that spread into human populations and the increase in the number of strains resistant to commonly used antibiotics (Abt et al., 2016; Dingle et al., 2017). The determination of a very large number of C. difficile genome sequences paints a picture of a rather diverse gene content of this species, with an estimated pan-genome of about 9600 genes but only a restricted (15–20%) core genome (Knight et al., 2015). The genus-level core genome includes about 550 protein families. Based on these data, a metabolic network comprising proteins, RNAs and metabolites has recently been constructed that is crucial for a deeper understanding of the varied biology and pathogenic potential of members of the genus Clostridium (Udaondo et al., 2017). C. difficile is a Gram-positive anaerobic spore-forming rod-shaped bacterium (Fig. 1) that can be found both in terrestrial and marine ecosystems and in the mammalian intestinal tract. Most human infants are colonized with it without exhibiting any negative symptoms, and the number of C. difficile carriers subsequently drops to about 3% in healthy adults (Bartlett and Perl, 2005). However, in hospital settings, a very large percentage of patients (20–40%) are carriers of C. difficile, and the ability of C. difficile to form highly stressand desiccation-resistant endospores (Fimlaid and Shen, 2015; Shen, 2015; Bhattacharjee et al., 2016) certainly contributes greatly to its dissemination in this environment and to the ensuing infection cycle (Abt et al., 2016). As a enteropathogen, C. difficile is a major cause of antibiotic-treatment-associated diarrhoea and the potentially deadly disease pseudomembranous colitis (Abt et al., 2016). Although great attention is focused on the considerable number of hospital acquired infections, the majority of reported cases of C. difficile infections actually occur outside clinical settings and in the absence of antibiotic use (Warriner et al., 2017), a treatment that fosters the colonization of the intestine by C. difficile (Shen, 2015; Abt et al., 2016). The sources of community-acquired C. difficile infections are open for debate but food-based reservoirs seem likely (Warriner et al., 2017). Since C. difficile is a strict anaerobe that used Stickland reactions for the generation of its energy, its metabolism needs to be carefully taken into considerations when issues related to its persistence in the environment, infection, and virulence are discussed (Bouillaut et al., 2015). Received 17 April, 2017; accepted 19 April, 2017. *For correspondence. E-mail bremer@staff.uni-marburg.de; Tel. (149)-64212821529; Fax (149)-6421-2828979.