scholarly journals The conserved serine transporter SdaC moonlights to enable self recognition

2021 ◽  
Author(s):  
Achala Chittor ◽  
Karine A. Gibbs
Keyword(s):  
Proteus Mirabilis ◽  
Sequence Variation ◽  
Interaction Network ◽  
Bacterial Survival ◽  
Ecological Constraints ◽  
Collective Behaviors ◽  
Open Conformation ◽  
Self Recognition ◽  
Recognition Protein ◽  
Recognition Systems

Cells can use self recognition to achieve cooperative behaviors. Self-recognition genes are thought to principally evolve in tandem with partner self-recognition alleles. However, other constraints on protein evolution could exist. Here, we have identified an interaction outside of self-recognition loci that could constrain the sequence variation of a self-recognition protein. We show that during collective swarm expansion in Proteus mirabilis , self-recognition signaling co-opts SdaC, a serine transporter. Serine uptake is crucial for bacterial survival and colonization. Single-residue variants of SdaC reveal that self recognition requires an open conformation of the protein; serine transport is dispensable. A distant ortholog from Escherichia coli is sufficient for self recognition; however, a paralogous serine transporter, YhaO, is not. Thus, SdaC couples self recognition and serine transport, likely through a shared molecular interface. Self recognition proteins may follow the framework of a complex interaction network rather than an isolated two-protein system. Understanding molecular and ecological constraints on self-recognition proteins lays the groundwork for insights into the evolution of self recognition and emergent collective behaviors. Importance Bacteria can receive secret messages from kin during migration. For Proteus mirabilis , these messages are necessary for virulence in multi-species infections. We show that a serine transporter—conserved among gamma-enterobacteria– enables self recognition. Molecular co-option of nutrient uptake could limit the sequence variation of these message proteins. SdaC is the primary transporter for L-serine, a vital metabolite for colonization during disease. Unlike many self-recognition receptors, SdaC is sufficiently conserved between species to achieve recognition. The predicted open conformation is shared by transport and recognition. SdaC reveals the interdependence of communication and nutrient acquisition. As the broader interactions of self-recognition proteins are studied, features shared among microbial self-recognition systems, such as Dictyostelium spp. and Neurospora spp., could emerge.

scholarly journals The conserved serine transporter SdaC moonlights to enable self recognition

2021 ◽  
Author(s):  
Achala Chittor ◽  
Karine A. Gibbs
Keyword(s):  
Escherichia Coli ◽  
Protein Evolution ◽  
Sequence Variation ◽  
Bacterial Survival ◽  
Ecological Constraints ◽  
Collective Behaviors ◽  
Open Conformation ◽  
Self Recognition ◽  
Recognition Protein ◽  
Cooperative Behaviors

AbstractCells can use self recognition to achieve cooperative behaviors. Self-recognition genes principally evolve in tandem with partner self-recognition alleles. However, other constraints on protein evolution could exist. Here, we have identified an interaction outside of self-recognition loci that could constrain the sequence variation of a self-recognition protein. We show that during collective swarm expansion in Proteus mirabilis, self-recognition signaling co-opts SdaC, a serine transporter. Serine uptake is crucial for bacterial survival and colonization. Single-residue variants of SdaC reveal that self recognition requires an open conformation of the protein; serine transport is dispensable. A distant ortholog from Escherichia coli is sufficient for self recognition; however, a homologous serine transporter, YhaO, is not. Thus, SdaC couples self recognition and serine transport, likely through a shared molecular interface. Understanding molecular and ecological constraints on self-recognition proteins can provide insights into the evolution of self recognition and emergent collective behaviors.Abstract Figure

scholarly journals Multilocus Self-Recognition Systems in Fungi as a Cause of Trans-Species Polymorphism

Genetics ◽  
2002 ◽  
Vol 161 (2) ◽  
pp. 633-641
Author(s):  
Christina A Muirhead ◽  
N Louise Glass ◽  
Montgomery Slatkin
Keyword(s):  
Genetic Model ◽  
Balancing Selection ◽  
Infectious Agents ◽  
Vegetative Compatibility Group ◽  
Vegetative Incompatibility ◽  
Hyphal Fusion ◽  
Self Recognition ◽  
Compatibility Group ◽  
Incompatibility Alleles ◽  
Recognition Systems

Abstract Trans-species polymorphism, meaning the presence of alleles in different species that are more similar to each other than they are to alleles in the same species, has been found at loci associated with vegetative incompatibility in filamentous fungi. If individuals differ at one or more of these loci (termed het for heterokaryon), they cannot form stable heterokaryons after vegetative fusion. At the het-c locus in Neurospora crassa and related species there is clear evidence of trans-species polymorphism: three alleles have persisted for ∼30 million years. We analyze a population genetic model of multilocus vegetative incompatibility and find the conditions under which trans-species polymorphism will occur. In the model, several unlinked loci determine the vegetative compatibility group (VCG) of an individual. Individuals of different VCGs fail to form productive heterokaryons, while those of the same VCG form viable heterokaryons. However, viable heterokaryon formation between individuals of the same VCG results in a loss in fitness, presumably via transfer of infectious agents by hyphal fusion or exploitation by aggressive genotypes. The result is a form of balancing selection on all loci affecting an individual's VCG. We analyze this model by making use of a Markov chain/strong selection, weak mutation (SSWM) approximation. We find that trans-species polymorphism of the type that has been found at the het-c locus is expected to occur only when the appearance of new incompatibility alleles is strongly constrained, because the rate of mutation to such alleles is very low, because the number of possible incompatibility alleles at each locus is restricted, or because the number of incompatibility loci is limited.

scholarly journals Peer pressure from a Proteus mirabilis self-recognition system controls participation in cooperative swarm motility:

2018 ◽  
Author(s):  
Murray J Tipping ◽  
Karine A Gibbs
Keyword(s):  
Proteus Mirabilis ◽  
Stringent Response ◽  
Peer Pressure ◽  
Opportunistic Pathogen ◽  
Recognition System ◽  
Kin Discrimination ◽  
Distinct Mechanism ◽  
Expression Of Genes ◽  
Self Recognition ◽  
Different Strains

Colonies of the opportunistic pathogen Proteus mirabilis can distinguish self from non-self: in swarming colonies of two different strains, one strain excludes the other from the expanding colony edge. Predominant models characterize bacterial kin discrimination as immediate antagonism towards non-kin cells, typically through delivery of toxin effector molecules from one cell into its neighbor. Upon effector delivery, receiving cells must either neutralize it by presenting a cognate anti-toxin, as would a clonal sibling, or suffer cell death or irreversible growth inhibition, as would a non-kin cell. Here we expand this paradigm to explain the non-lethal Ids self-recognition system, which stops access to a cooperative social behavior in P. mirabilis through a distinct mechanism: selectively and transiently inducing non-self cells into a lifestyle incompatible with cooperative swarming. This state is characterized by reduced expression of genes associated with protein synthesis, virulence, and motility, and also causes non-self cells to tolerate previously lethal concentrations of antibiotics. We found that entry into this state requires a temporary activation of the stringent response in non-self cells and results in the iterative exclusion of non-self cells as a swarm colony migrates outwards. These data clarify the intricate connection between non-lethal recognition and the lifecycle of P. mirabilis swarm colonies.

scholarly journals Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations

2016 ◽  
Author(s):  
Amrita Roy ◽  
Liangzhong Lim ◽  
Shagun Srivastava ◽  
Jianxing Song
Keyword(s):  
Sequence Variation ◽  
Md Simulations ◽  
World Population ◽  
Nmr Studies ◽  
Allosteric Inhibitors ◽  
Open Conformation ◽  
C Terminus ◽  
Β Sheet ◽  
Insight Into ◽  
Close Contacts

ABSTRACTZika virus can be passed from a pregnant woman to her fetus, thus leading to birth defects including more than microcephaly. It has been recently estimated that one-third of the world population will be infected by Zika, but unfortunately no vaccine or medicine is available so far. Zika NS2B-NS3pro is essential for its replication and thus represents an attractive target for drug discovery/design. Here we characterized conformation, catalysis, inhibition and dynamics of linked and unlinked Zika NS2B-NS3pro complexes by both experiments and MD simulations. The results unveil the unique properties of Zika NS2B-NS3pro which are very different from Dengue one. Particularly, CD and NMR studies indicate that unlike Dengue, the C-terminal region of Zika NS2B with a significant sequence variation is highly disordered in the open conformation. Indeed, MD simulations reveal that up to 100 ns, the Dengue NS2B C-terminus constantly has close contacts with its NS3pro domain. By a sharp contrast, the Zika NS2B C-terminus loses the contacts with its NS3pro domain after 10 ns, further forming a short β-sheet characteristic of the closed conformation at 30 ns. Furthermore, we found that a small molecule, previously identified as an active site inhibitor for other flaviviral NS2B-NS3pro, inhibited Zika NS2B-NS3pro potently in an allosteric manner. Our study provides the first insight into the dynamics of Zika NS2B-NS3pro and further deciphers that it is susceptible to allosteric inhibition, which thus bears critical implications for the future development of therapeutic allosteric inhibitors.

scholarly journals A single point mutation in a TssB/VipA homolog disrupts sheath formation in the type VI secretion system of Proteus mirabilis

2017 ◽  
Author(s):  
Christina C. Saak ◽  
Martha A. Zepeda-Rivera ◽  
Karine A. Gibbs
Keyword(s):  
Proteus Mirabilis ◽  
Single Point ◽  
Single Amino Acid ◽  
Single Point Mutation ◽  
Type Vi Secretion System ◽  
Self Identity ◽  
Type Vi Secretion ◽  
Self Recognition ◽  
Single Amino Acid Change ◽  
Sheath Formation

AbstractThe type VI secretion (T6S) system is a molecular device for the delivery of proteins from one cell into another. T6S function depends on the contractile sheath comprised of TssB/VipA and TssC/VipB proteins. We previously reported on a mutant variant of TssB that disrupts T6S-dependent export of the self-identity protein, IdsD, in the bacterium Proteus mirabilis. Here we determined the mechanism underlying that initial observation. We show that T6S-dependent export of multiple self-recognition proteins is abrogated in this mutant strain. We have mapped the mutation, which is a single amino acid change, to a region predicted to be involved in the formation of the TssB-TssC sheath. We have demonstrated that this mutation does indeed inhibit sheath formation, thereby explaining the global disruption of T6S activity. We propose that this mutation could be utilized as an important tool for studying functions and behaviors associated with T6S systems.

scholarly journals Analogies in the evolution of individual and social immunity

2008 ◽  
Vol 364 (1513) ◽  
pp. 129-142 ◽  
Author(s):  
Sylvia Cremer ◽  
Michael Sixt
Keyword(s):  
Immune Responses ◽  
Germ Line ◽  
The Body ◽  
Reproductive Tissue ◽  
Defence Mechanisms ◽  
Self Recognition ◽  
Insect Societies ◽  
The Social ◽  
Recognition Systems ◽  
Multicellular Organisms

We compare anti-parasite defences at the level of multicellular organisms and insect societies, and find that selection by parasites at these two organisational levels is often very similar and has created a number of parallel evolutionary solutions in the host's immune response. The defence mechanisms of both individuals and insect colonies start with border defences to prevent parasite intake and are followed by soma defences that prevent the establishment and spread of the parasite between the body's cells or the social insect workers. Lastly, germ line defences are employed to inhibit infection of the reproductive tissue of organisms or the reproductive individuals in colonies. We further find sophisticated self/non-self-recognition systems operating at both levels, which appear to be vital in maintaining the integrity of the body or colony as a reproductive entity. We then expand on the regulation of immune responses and end with a contemplation of how evolution may shape the different immune components, both within and between levels. The aim of this review is to highlight common evolutionary principles acting in disease defence at the level of both individual organisms and societies, thereby linking the fields of physiological and ecological immunology.

Sign in / Sign up

Export Citation Format

Share Document