Carnitine in bacterial physiology and metabolism

Abstract

Carnitine is a quaternary amine compound found at high concentration in animal tissues, particularly muscle, and is most well studied for its contribution to fatty acid transport into mitochondria. In bacteria, carnitine is an important osmoprotectant, and can also enhance thermotolerance, cryotolerance and barotolerance. Carnitine can be transported into the cell or acquired from metabolic precursors, where it can serve directly as a compatible solute for stress protection or be metabolized through one of a few distinct pathways as a nutrient source. In this review, we summarize what is known about carnitine physiology and metabolism in bacteria. In particular, recent advances in the aerobic and anaerobic metabolic pathways as well as the use of carnitine as an electron acceptor have addressed some long-standing questions in the field. Received 5 January 2015 Accepted 17 March 2015Introduction Carnitine (c-trimethylamino-b-hydroxybutyric acid) ( Fig. 1) is a quaternary amine compound that can be produced by all domains of life, and was discovered in muscle extract in 1905 by Gulewitsch & Krimberg (1905) and Kutscher (1905). It was shown to be essential for larval development of the mealworm Tenebrio molitor and was originally designated vitamin B T based on this requirement. Later, it was discovered that carnitine can be synthesized in mammals and is now considered to be a quasi-nutrient or conditionally essential nutrient (Flanagan et al., 2010), as neonates have reduced biosynthesis and rely on placental transfer of carnitine in utero and exogenous sources after birth (Combs, 2012). Fifty years after the discovery of carnitine, it was demonstrated that assorted Gram-positive and Gram-negative bacteria could use carnitine in either aerobic or anaerobic environments for a variety of cellular functions, including as an electron acceptor, as a compatible solute to survive environmental insults or as a sole carbon, nitrogen and energy source. Bacterial carnitine metabolism was most recently reviewed in 1998 (Bieber, 1988;Bremer, 1983;Kleber, 1997;Rebouche & Seim, 1998) and the field has seen important advances. This review summarizes what we knew at the time of the previous reviews and emphasizes what we have learned since, including: (i) how anaerobic bacteria synthesize and utilize crotonobetaine and carnitine as final electron acceptors, (ii) the impact of carnitine degradation by the intestinal microbiota and the genes responsible for this anaerobic conversion, (iii) the genes involved in aerobic degradation of carnitine, and (iv) how carnitine as a compatible solute impacts survival within and outside of the host. Carnitine in the environmentRecent work makes it clear that while animals represent the most readily accessible source of carnitine, carnitine is often present and sometimes abundant in soil and natural waters. Quaternary ammonium compounds are abundant in a number of soil ecosystems, including comprising a quarter of the most abundant organic nitrogen compounds in the soil water of a subalpine gras...

Identification and characterization of a carnitine transporter in Acinetobacter baumannii

“…We confirmed that A. baumannii uses carnitine as sole carbon and energy source. This together with the abundance of carnitine in the human host (Meadows & Wargo, ) suggests that carnitine is important for metabolic adaptation of A. baumannii to the human host. However, this might only be one physiological benefit of carnitine for A. baumannii .…”

“…The uptake of both choline and carnitine by a classical member of the BCCT family is quite unique and without precedence. Carnitine transport and metabolism have already been thoroughly studied in different bacteria such as Pseudomonas aeruginosa and in members of the Enterobacteriaceae (Meadows & Wargo, ). In P. aeruginosa, carnitine is imported by an ABC transporter and can be used as sole carbon and nitrogen source but also plays a role in osmoprotection and virulence factor induction (Chen, Malek, Wargo, Hogan, & Beattie, ; Kleber, Schöpp, Sorger, Tauchert, & Aurich, ; Lucchesi et al, ; Wargo & Hogan, ).…”

Epigenetic findings in periodontitis in UK twins: a cross sectional study

“…The strongest signal was observed for ornithine ( p -value = 0.008), which is also significantly associated with tooth mobility ( p -value = 0.012). The remaining metabolites also included 3-dehydrocarnitine, ranked fifth ( p -value = 0.029), which is consumed by gram negative and positive bacteria in either aerobic or anaerobic environmental insults or as a sole carbon, nitrogen and energy source [24].…”

Phylogeny-corrected identification of microbial gene families relevant to human gut colonization

“…Indeed, bile acids are metabolites of cholesterol that are produced by vertebrates and thus unlikely to be encountered outside of the host. While the metabolite L-carnitine is made and used in organisms spanning the tree of life, it is particularly concentrated in animal tissue and especially red meat, and cannot be further catabolized by humans [43], making it available to intestinal microbes. Bile acid transformation by gut commensals is a well-established function of the gut microbiome, with complex influences on health (reviewed in Staley et al [44]).…”