Intracellular Bacteria Survival Strategies

Intracellular Bacteria Survival Strategies Survival strategies of intracellular bacteria to amoeba grazing Free living amoebae are unicellular protozoan that are ubiquitous in various environments. They mainly feed on bacteria through phagocytosis, and kill them in phagosome, which is a harsh acidic environment that contains different antimicrobial weapons. Amoebae grazing has been suggested to be one of the major forces that shaping bacterial abundance and diversity. However, some bacteria have developed strategies to survive phagocytosis by free-living amoebae and are able to exploit host cell resources. Below we try to summarize our current knowledge on the diverse mechanisms that are used by intracellular pathogens to overcome amoebae defenses. The most obvious strategy is to escape from the phagosome so that intracellular pathogens can avoid amoebae killing. Because phagosome is generally viewed as a harsh environment where ingested bacteria are confronted with acidification, oxidative burst, nutrient deprivation, and various antimicrobial small molecules. For instance, some members of the genus Mycobacterium, such as Mycobacterium marinum and M. tuberculosis, have evolved the ability to escape from phagosome into the host cytosol. This process requires the mycobaterial type VII secretion system ESX-1. In addition, both M. marinum and M. tuberculosis can be ejected from the cell through an F-actin structure ejectosome to spread cell to cell [1,2]. In general, cytosol is considered as permissive for bacterial growth, as it provides nutrients and is protected from host immune killing [3]. Therefore it is an ideal place for bacteria to thrive after escaping from phagosome. However, some intracellular pathogens can invade more unusual intracellular niches such as the eukaryotic nucleus. This includes in the free living amoebae Naegleria clarki [4] and more recently in another amoeba strain Hartmannella sp. [5]. These so called intranuclear bacteria are relatively rare and current studies suggest an independent evolutionary origin of an intranuclear life style. Taken together, after escaping intracellular bacteria can live in either cytosol or nucleus. The second strategy is to stay within the phagosomal vacuole, but subvert its antimicrobial mechanisms. These include preventing phagosome-lysosome fusion, modulating phagosomal pH, damaging phagosomal membranes, and/or quenching oxidative bursts [6]. Intracellular pathogens can utilize a combination of these approaches. For instance, Legionella pneumophila has evolved a complex system which allows the bacteria to hijack the phagocytic vacuole [7]. It can evade the endocytic pathway and the subsequent phagosome-lysosome fusion, delays its acidification and establishes a safe intracellular niche called Legionella containing vacuole (LCV), which allows intracellular replication [7,8]. Further studies suggest that L. pneumophila uses the Icm/Dot type IV secretion system (T4SS) and the Lsp type II secretion system (T2SS) to avoid killing and exploit host resources [7,9]. There are plenty of other bacteria using similar strategies [10]. However, a very special case is that some intracellu lar pathogens can exploit the complex cycle of the social amoeba. In the amoeba farming symbiosis, our lab group has found that some wild Dictyostelium discoideum clones stably associate with different bacterial partners and use them as food and weapons [11-14]. These clones are called farmers because they can seed and harvest their crops in new environments [14]. In addition, two clades of inedible Burkholderia bacteria have been found to induce farming, causing the amoeba host to carry them, along with edible crop bacteria [11]. Another recent case shows that Bordetella bronchiseptica can also exploit the complex life cycle of D. discoideum. Interestingly, B. bronchiseptica resides outside the D. discoideum spores, while the carried Burkholderia localize both inside and outside of spores, indicating these two bacteria have different exit strategies. Overall, the majority of intracellular pathogens occupy phagosomal vacuole, while only some are able to escape the phagosome [6]. This is possibly due to the fact that specialized mechanisms are needed to escape from phagosome [3,6]. There is no clear relationship between the type of survival strategies and whether the microbe is an obligate or facultative intracellular pathogen [6]. References 1. 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