Abstract
Many Gram-negative bacteria use a type VI secretion system (T6SS) for microbial warfare and/or host manipulation. Acinetobacter baumannii is an important nosocomial pathogen and many A. baumannii strains utilize a T6SS to deliver toxic effector proteins to surrounding bacterial cells. These toxic effectors are usually delivered together with VgrG proteins, which form part of the T6SS tip complex. All previously identified A. baumannii T6SS effectors are encoded within a three- or four-gene locus that also encodes a cognate VgrG and immunity protein, and sometimes a chaperone. In order to characterize the diversity and distribution of T6SS effectors and immunity proteins in this species, we first identified all vgrG genes in 97 A. baumannii strains via the presence of the highly conserved VgrG domain. Most strains encoded between two and four different VgrG proteins. We then analyzed the regions downstream of the identified vgrG genes and identified more than 240 putative effectors. The presence of conserved domains in these effectors suggested a range of functions, including peptidoglycan hydrolases, lipases, nucleases, and nucleic acid deaminases. However, 10 of the effector groups had no functionally characterized domains. Phylogenetic analysis of these putative effectors revealed that they clustered into 32 distinct groups that appear to have been acquired from a diverse set of ancestors. Corresponding immunity proteins were identified for all but two of the effector groups. Effectors from eight of the 32 groups contained N-terminal rearrangement hotspot (RHS) domains. The C-terminal regions of these RHS proteins, which are predicted to confer the toxic effector function, were very diverse, but the N-terminal RHS domains clustered into just two groups. While the majority of A. baumannii strains contained an RHS type effector, no strains encoded two RHS effectors with similar N-terminal sequences, suggesting that the presence of similar N-terminal RHS domains leads to competitive exclusion. Together, these analyses define the extreme diversity of T6SS effectors within A. baumannii and, as many have unknown functions, future detailed characterization of these effectors may lead to the identification of proteins with novel antibacterial properties.
Highlights
Acinetobacter baumannii, is a rapidly emerging, multi-drug resistant, nosocomial pathogen with no clearly defined environmental niche
We propose altering the names of the cognate VgrG, chaperone, and immunity proteins according to the naming of the effectors, with VgrG proteins identified with a number corresponding to the cognate effector, chaperone proteins identified as T6SS accessory proteins (Tap) with a number corresponding to the cognate effector and immunity proteins becoming T6SS immunity with an appropriate middle letter determined by the cognate effector function (e.g., VgrG2 and Rhs2I from A. baumannii AB307-0294 become VgrG16 and Tdi16AB, respectively)
We identified genes predicted to encode 272 VgrG proteins, 244 putative effectors and 228 immunity proteins
Summary
Acinetobacter baumannii, is a rapidly emerging, multi-drug resistant, nosocomial pathogen with no clearly defined environmental niche. The T6SS is a complex nanomachine that can deliver effector proteins into the extracellular environment or directly into eukaryotic or prokaryotic cells (Cianfanelli et al, 2016b). Effectors that target eukaryotic cells generally manipulate the host cell to increase the survival of the invading pathogen, while effectors that target prokaryotic cells generally kill surrounding susceptible bacteria (prey) and provide a competitive advantage for the bacteria that delivered the effector (predator) (Cianfanelli et al, 2016b). The ability of a T6SS-positive predator to successfully target and kill another bacterium is dependent on the specificity of the effectors delivered by the predator and/or the particular T6SS components (e.g., specific immunity proteins) produced by the prey cell (Miyata et al, 2013; Alcoforado Diniz and Coulthurst, 2015). Two effectors have recently been identified that are toxic to Candida albicans, the first T6SS effectors with direct antifungal activity (Trunk et al, 2018)
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