Abstract
The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionella nucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms.
Highlights
Legionella pneumophila is an intracellular pathogen and the major causative agent of Legionnaire’s disease, an acute form of pneumonia
Mitochondrial carrier proteins evolved during endosymbiosis to transport substrates across the mitochondrial inner membrane
We named the mitochondrial carrier protein from L. pneumophila Legionella nucleotide carrier Protein (LncP) and determined that the protein is translocated into host cells during infection by the bacterial Dot/Icm type IV secretion system
Summary
Legionella pneumophila is an intracellular pathogen and the major causative agent of Legionnaire’s disease, an acute form of pneumonia. The ability of the bacteria to replicate in environmental protozoa such as amoebae has equipped the bacteria with the capacity to replicate in human alveolar macrophages, leading to lung inflammation and disease [1,2]. The bacteria replicate within a membrane bound vacuole, block phagolysosome fusion and intercept vesicles trafficking in the secretory pathway [3,4]. Formation of the intracellular replicative niche of L. pneumophila results from extensive remodelling of the intracellular vacuole and multiple interactions with vesicle trafficking pathways within the host cell [8,9]
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