scholarly journals Cyclic AMP Regulates Social Behavior in African Trypanosomes

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Michael Oberholzer ◽  
Edwin A. Saada ◽  
Kent L. Hill
Keyword(s):  
Social Behavior ◽  
Cyclic Amp ◽  
Protozoan Parasite ◽  
Wild Type ◽  
Protozoan Parasites ◽  
Content Type ◽  
African Trypanosomes ◽  
Signaling Systems ◽  
Extracellular Signals ◽  
Social Motility

ABSTRACT The protozoan parasite Trypanosoma brucei engages in surface-induced social behavior, termed social motility, characterized by single cells assembling into multicellular groups that coordinate their movements in response to extracellular signals. Social motility requires sensing and responding to extracellular signals, but the underlying mechanisms are unknown. Here we report that T. brucei social motility depends on cyclic AMP (cAMP) signaling systems in the parasite's flagellum (synonymous with cilium). Pharmacological inhibition of cAMP-specific phosphodiesterase (PDE) completely blocks social motility without impacting the viability or motility of individual cells. Using a fluorescence resonance energy transfer (FRET)-based sensor to monitor cAMP dynamics in live cells, we demonstrate that this block in social motility correlates with an increase in intracellular cAMP levels. RNA interference (RNAi) knockdown of the flagellar PDEB1 phenocopies pharmacological PDE inhibition, demonstrating that PDEB1 is required for social motility. Using parasites expressing distinct fluorescent proteins to monitor individuals in a genetically heterogeneous community, we found that the social motility defect of PDEB1 knockdowns is complemented by wild-type parasites in trans. Therefore, PDEB1 knockdown cells are competent for social motility but appear to lack a necessary factor that can be provided by wild-type cells. The combined data demonstrate that the role of cyclic nucleotides in regulating microbial social behavior extends to African trypanosomes and provide an example of transcomplementation in parasitic protozoa. IMPORTANCE In bacteria, studies of cell-cell communication and social behavior have profoundly influenced our understanding of microbial physiology, signaling, and pathogenesis. In contrast, mechanisms underlying social behavior in protozoan parasites are mostly unknown. Here we show that social behavior in the protozoan parasite Trypanosoma brucei is governed by cyclic-AMP signaling systems in the flagellum, with intriguing parallels to signaling systems that control bacterial social behavior. We also generated a T. brucei social behavior mutant and found that the mutant phenotype is complemented by wild-type cells grown in the same culture. Our findings open new avenues for dissecting social behavior and signaling in protozoan parasites and illustrate the capacity of these organisms to influence each other's behavior in mixed communities.

scholarly journals Global Analysis of Protein Palmitoylation in African Trypanosomes

2010 ◽  
Vol 10 (3) ◽  
pp. 455-463 ◽  
Author(s):  
Brian T. Emmer ◽  
Ernesto S. Nakayasu ◽  
Christina Souther ◽  
Hyungwon Choi ◽  
Tiago J. P. Sobreira ◽  
...  
Keyword(s):  
Protein Identification ◽  
Global Analysis ◽  
Large Family ◽  
Protozoan Parasite ◽  
Selective Inhibition ◽  
Content Type ◽  
African Trypanosomes ◽  
Rich Domain ◽  
Protein Palmitoylation ◽  
Liquid Chromatography Tandem Mass

ABSTRACT Many eukaryotic proteins are posttranslationally modified by the esterification of cysteine thiols to long-chain fatty acids. This modification, protein palmitoylation, is catalyzed by a large family of palmitoyl acyltransferases that share an Asp-His-His-Cys Cys-rich domain but differ in their subcellular localizations and substrate specificities. In Trypanosoma brucei , the flagellated protozoan parasite that causes African sleeping sickness, protein palmitoylation has been observed for a few proteins, but the extent and consequences of this modification are largely unknown. We undertook the present study to investigate T. brucei protein palmitoylation at both the enzyme and substrate levels. Treatment of parasites with an inhibitor of total protein palmitoylation caused potent growth inhibition, yet there was no effect on growth by the separate, selective inhibition of each of the 12 individual T. brucei palmitoyl acyltransferases. This suggested either that T. brucei evolved functional redundancy for the palmitoylation of essential palmitoyl proteins or that palmitoylation of some proteins is catalyzed by a noncanonical transferase. To identify the palmitoylated proteins in T. brucei , we performed acyl biotin exchange chemistry on parasite lysates, followed by streptavidin chromatography, two-dimensional liquid chromatography-tandem mass spectrometry protein identification, and QSpec statistical analysis. A total of 124 palmitoylated proteins were identified, with an estimated false discovery rate of 1.0%. This palmitoyl proteome includes all of the known palmitoyl proteins in procyclic-stage T. brucei as well as several proteins whose homologues are palmitoylated in other organisms. Their sequences demonstrate the variety of substrate motifs that support palmitoylation, and their identities illustrate the range of cellular processes affected by palmitoylation in these important pathogens.

scholarly journals Cross Talk between the Cell Wall Integrity and Cyclic AMP/Protein Kinase A Pathways in Cryptococcus neoformans

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Maureen J. Donlin ◽  
Rajendra Upadhya ◽  
Kimberly J. Gerik ◽  
Woei Lam ◽  
Laura G. VanArendonk ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Cryptococcus Neoformans ◽  
Signaling Pathway ◽  
Cell Wall Integrity ◽  
Wild Type ◽  
Content Type ◽  
Kinase A

ABSTRACTCryptococcus neoformans is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis ofC. neoformans, and biosynthesis and repair of the wall is primarily controlled by the cell wall integrity (CWI) signaling pathway. Previous work has shown that deletion of genes encoding the four major kinases in the CWI signaling pathway, namely,PKC1,BCK1,MKK2, andMPK1results in severe cell wall phenotypes, sensitivity to a variety of cell wall stressors, and for Mpk1, reduced virulence in a mouse model. Here, we examined the global transcriptional responses to gene deletions ofBCK1,MKK2, andMPK1compared to wild-type cells. We found that over 1,000 genes were differentially expressed in one or more of the deletion strains, with 115 genes differentially expressed in all three strains, many of which have been identified as genes regulated by the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. Biochemical measurements of cAMP levels in the kinase deletion strains revealed significantly less cAMP in all of the deletion strains compared to the wild-type strain. The deletion strains also produced significantly smaller capsules than the wild-type KN99 strain did under capsule-inducing conditions, although the levels of capsule they shed were similar to those shed by the wild type. Finally, addition of exogenous cAMP led to reduced sensitivity to cell wall stress and restored surface capsule to levels near those of wild type. Thus, we have direct evidence of cross talk between the CWI and cAMP/PKA pathways that may have important implications for regulation of cell wall and capsule homeostasis.IMPORTANCECryptococcus neoformans is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis ofC. neoformans, and biosynthesis and repair of the wall are primarily controlled by the cell wall integrity (CWI) signaling pathway. In this study, we demonstrate that deletion of any of three core kinases in the CWI pathway impacts not only the cell wall but also the amount of surface capsule. Deletion of any of the kinases results in significantly reduced cellular cyclic AMP (cAMP) levels, and addition of exogenous cAMP rescues the capsule defect and some cell wall defects, supporting a direct role for the CWI pathway in regulation of capsule in conjunction with the cAMP/protein kinase A pathway.

scholarly journals The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions

2016 ◽  
Vol 198 (16) ◽  
pp. 2263-2274 ◽  
Author(s):  
Ryan N. C. Buensuceso ◽  
Ylan Nguyen ◽  
Kun Zhang ◽  
Martin Daniel-Ivad ◽  
Seiji N. Sugiman-Marangos ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Tetratricopeptide Repeat ◽  
Twitching Motility ◽  
Wild Type ◽  
Inner Membrane ◽  
Content Type ◽  
Terminal Domain ◽  
C Terminus ◽  
Independent Functions

ABSTRACTFimV is aPseudomonas aeruginosainner membrane protein that regulates intracellular cyclic AMP (cAMP) levels—and thus type IV pilus (T4P)-mediated twitching motility and type II secretion (T2S)—by activating the adenylate cyclase CyaB. Its cytoplasmic domain contains three predicted tetratricopeptide repeat (TPR) motifs separated by an unstructured region: two proximal to the inner membrane and one within the “FimV C-terminal domain,” which is highly conserved across diverse homologs. Here, we present the crystal structure of the FimV C terminus, FimV861–919, containing a TPR motif decorated with solvent-exposed, charged side chains, plus a C-terminal capping helix. FimV689, a truncated form lacking this C-terminal motif, did not restore wild-type levels of twitching or surface piliation compared to the full-length protein. FimV689failed to restore wild-type levels of the T4P motor ATPase PilU or T2S, suggesting that it was unable to activate cAMP synthesis. Bacterial two-hybrid analysis showed that TPR3 interacts directly with the CyaB activator, FimL. However, FimV689failed to restore wild-type motility in afimVmutant expressing a constitutively active CyaB (fimV cyaB-R456L), suggesting that the C-terminal motif is also involved in cAMP-independent functions of FimV. The data show that the highly conserved TPR-containing C-terminal domain of FimV is critical for its cAMP-dependent and -independent functions.IMPORTANCEFimV is important for twitching motility and cAMP-dependent virulence gene expression inP. aeruginosa. FimV homologs have been identified in several human pathogens, and their functions are not limited to T4P expression. The C terminus of FimV is remarkably conserved among otherwise very diverse family members, but its role is unknown. We provide here biological evidence for the importance of the C-terminal domain in both cAMP-dependent (through FimL) and -independent functions of FimV. We present X-ray crystal structures of the conserved C-terminal domain and identify a consensus sequence for the C-terminal TPR within the conserved domain. Our data extend our knowledge of FimV's functionally important domains, and the structures and consensus sequences provide a foundation for studies of FimV and its homologs.

scholarly journals Mass Spectrometric Analysis of l-Cysteine Metabolism: Physiological Role and Fate of l-Cysteine in the Enteric Protozoan Parasite Entamoeba histolytica

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Ghulam Jeelani ◽  
Dan Sato ◽  
Tomoyoshi Soga ◽  
Haruo Watanabe ◽  
Tomoyoshi Nozaki
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Carboxylic Acid ◽  
Stable Isotope ◽  
Carboxylic Acids ◽  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Protozoan Parasites ◽  
Metabolic Fate ◽  
Content Type

ABSTRACTl-Cysteine is essential for virtually all living organisms, from bacteria to higher eukaryotes. Besides having a role in the synthesis of virtually all proteins and of taurine, cysteamine, glutathione, and other redox-regulating proteins,l-cysteine has important functions under anaerobic/microaerophilic conditions. In anaerobic or microaerophilic protozoan parasites, such asEntamoeba histolytica,l-cysteine has been implicated in growth, attachment, survival, and protection from oxidative stress. However, a specific role of this amino acid or related metabolic intermediates is not well understood. In this study, using stable-isotope-labeledl-cysteine and capillary electrophoresis-time of flight mass spectrometry, we investigated the metabolism ofl-cysteine inE. histolytica. [U-13C3,15N]l-cysteine was rapidly metabolized into three unknown metabolites, besidesl-cystine andl-alanine. These metabolites were identified as thiazolidine-4-carboxylic acid (T4C), 2-methyl thiazolidine-4-carboxylic acid (MT4C), and 2-ethyl-thiazolidine-4-carboxylic acid (ET4C), the condensation products ofl-cysteine with aldehydes. We demonstrated that these 2-(R)-thiazolidine-4-carboxylic acids serve for storage ofl-cysteine. Liberation ofl-cysteine occurred when T4C was incubated with amebic lysates, suggesting enzymatic degradation of thesel-cysteine derivatives. Furthermore, T4C and MT4C significantly enhanced trophozoite growth and reduced intracellular reactive oxygen species (ROS) levels when it was added to cultures, suggesting that 2-(R)-thiazolidine-4-carboxylic acids are involved in the defense against oxidative stress.IMPORTANCEAmebiasis is a human parasitic disease caused by the protozoan parasiteEntamoeba histolytica. In this parasite,l-cysteine is the principal low-molecular-weight thiol and is assumed to play a significant role in supplying the amino acid during trophozoite invasion, particularly when the parasites move from the anaerobic intestinal lumen to highly oxygenated tissues in the intestine and the liver. It is well known thatE. histolyticaneeds a comparatively high concentration ofl-cysteine for its axenic cultivation. However, the reason for and the metabolic fate ofl-cysteine in this parasite are not well understood. Here, using a metabolomic and stable-isotope-labeled approach, we investigated the metabolic fate of this amino acid in these parasites. We found thatl-cysteine inside the cell rapidly reacts with aldehydes to form 2-(R)-thiazolidine-4-carboxylic acid. We showed that these 2-(R)-thiazolidine-4-carboxylic derivatives serve as anl-cysteine source, promote growth, and protect cells against oxidative stress by scavenging aldehydes and reducing the ROS level. Our findings represent the first demonstration of 2-(R)-thiazolidine-4-carboxylic acids and their roles in protozoan parasites.

scholarly journals Interleukin-10 from T Cells, but Not Macrophages and Granulocytes, Is Required for Chronic Disease in Leishmania mexicana Infection

2015 ◽  
Vol 83 (4) ◽  
pp. 1366-1371 ◽  
Author(s):  
Laurence U. Buxbaum
Keyword(s):  
T Cells ◽  
Chronic Disease ◽  
Indirect Evidence ◽  
Protozoan Parasite ◽  
Interleukin 10 ◽  
Parasite Control ◽  
Leishmania Mexicana ◽  
Wild Type ◽  
Indirect Pathway ◽  
Content Type

Chronic cutaneous disease of mice caused by the protozoan parasiteLeishmania mexicanarequires interleukin-10 (IL-10) and FcγRIII (an activating IgG receptor). Macrophages readily secrete IL-10 in response to IgG-coated amastigotes, making macrophages a prime candidate as the critical source of IL-10. However, indirect evidence suggested that macrophage IL-10 is not essential for chronic disease. I now show directly that mice lacking IL-10 from macrophages and granulocytes still have chronic disease, like wild-type C57BL/6 mice. However, T cell-derived IL-10 is required for chronic disease. CD4-cre IL-10flox/floxmice lack IL-10 from T cells (both CD4+and CD8+) and heal theirL. mexicanalesions, with parasite control. I had previously shown that depletion of CD25+T cells had no effect on chronic disease, and thus, T cells other than CD25+regulatory T (Treg) cells should be the important source of IL-10. Given that conventional T cells do not express FcγRs, there is likely to be an indirect pathway by which FcγRIII on some other cell engaged by IgG1-amastigote immune complexes induces IL-10 from T cells. Further work is needed to delineate these pathways.

scholarly journals Insect Stage-Specific Adenylate Cyclases Regulate Social Motility in African Trypanosomes

2014 ◽  
Vol 14 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Miguel A. Lopez ◽  
Edwin A. Saada ◽  
Kent L. Hill
Keyword(s):  
Adenylate Cyclase ◽  
Drug Targets ◽  
Catalytic Domain ◽  
Cell Communication ◽  
Tsetse Fly ◽  
Microbial Pathogens ◽  
Group Level ◽  
Content Type ◽  
African Trypanosomes ◽  
Social Motility

ABSTRACTSophisticated systems for cell-cell communication enable unicellular microbes to act as multicellular entities capable of group-level behaviors that are not evident in individuals. These group behaviors influence microbe physiology, and the underlying signaling pathways are considered potential drug targets in microbial pathogens.Trypanosoma bruceiis a protozoan parasite that causes substantial human suffering and economic hardship in some of the most impoverished regions of the world.T. bruceilives on host tissue surfaces during transmission through its tsetse fly vector, and cultivation on surfaces causes the parasites to assemble into multicellular communities in which individual cells coordinate their movements in response to external signals. This behavior is termed “social motility,” based on its similarities with surface-induced social motility in bacteria, and it demonstrates that trypanosomes are capable of group-level behavior. Mechanisms governingT. bruceisocial motility are unknown. Here we report that a subset of receptor-type adenylate cyclases (ACs) in the trypanosome flagellum regulate social motility. RNA interference-mediated knockdown of adenylate cyclase 6 (AC6), or dual knockdown of AC1 and AC2, causes a hypersocial phenotype but has no discernible effect on individual cells in suspension culture. Mutation of the AC6 catalytic domain phenocopies AC6 knockdown, demonstrating that loss of adenylate cyclase activity is responsible for the phenotype. Notably, knockdown of other ACs did not affect social motility, indicating segregation of AC functions. These studies reveal interesting parallels in systems that control social behavior in trypanosomes and bacteria and provide insight into a feature of parasite biology that may be exploited for novel intervention strategies.

scholarly journals Cyclic AMP Effectors in African Trypanosomes Revealed by Genome-Scale RNA Interference Library Screening for Resistance to the Phosphodiesterase Inhibitor CpdA

2013 ◽  
Vol 57 (10) ◽  
pp. 4882-4893 ◽  
Author(s):  
Matthew K. Gould ◽  
Sabine Bachmaier ◽  
Juma A. M. Ali ◽  
Sam Alsford ◽  
Daniel N. A. Tagoe ◽  
...  
Keyword(s):  
Rna Interference ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Cross Resistance ◽  
Mammalian Host ◽  
Content Type ◽  
African Trypanosomes ◽  
A Genome ◽  
Camp Levels ◽  
Trypanocidal Drugs

ABSTRACTOne of the most promising new targets for trypanocidal drugs to emerge in recent years is the cyclic AMP (cAMP) phosphodiesterase (PDE) activity encoded byTbrPDEB1andTbrPDEB2. These genes were genetically confirmed as essential, and a high-affinity inhibitor, CpdA, displays potent antitrypanosomal activity. To identify effectors of the elevated cAMP levels resulting from CpdA action and, consequently, potential sites for adaptations giving resistance to PDE inhibitors, resistance to the drug was induced. Selection of mutagenized trypanosomes resulted in resistance to CpdA as well as cross-resistance to membrane-permeable cAMP analogues but not to currently used trypanocidal drugs. Resistance was not due to changes in cAMP levels or inPDEBgenes. A second approach, a genome-wide RNA interference (RNAi) library screen, returned four genes giving resistance to CpdA upon knockdown. Validation by independent RNAi strategies confirmed resistance to CpdA and suggested a role for the identifiedcAMPResponseProteins (CARPs) in cAMP action. CARP1 is unique to kinetoplastid parasites and has predicted cyclic nucleotide binding-like domains, and RNAi repression resulted in >100-fold resistance. CARP2 and CARP4 are hypothetical conserved proteins associated with the eukaryotic flagellar proteome or with flagellar function, with an orthologue of CARP4 implicated in human disease. CARP3 is a hypothetical protein, unique toTrypanosoma. CARP1 to CARP4 likely represent components of a novel cAMP signaling pathway in the parasite. As cAMP metabolism is validated as a drug target inTrypanosoma brucei, cAMP effectors highly divergent from the mammalian host, such asCARP1, lend themselves to further pharmacological development.

scholarly journals Heme Uptake Mediated by LHR1 Is Essential for Leishmania amazonensis Virulence

2013 ◽  
Vol 81 (10) ◽  
pp. 3620-3626 ◽  
Author(s):  
Danilo C. Miguel ◽  
Andrew R. Flannery ◽  
Bidyottam Mittra ◽  
Norma W. Andrews
Keyword(s):  
Transmembrane Protein ◽  
Protozoan Parasite ◽  
Leishmania Amazonensis ◽  
Ferric Reductase ◽  
Wild Type ◽  
Heme Uptake ◽  
Intracellular Growth ◽  
Cutaneous Lesions ◽  
Content Type ◽  
Single Knockout

ABSTRACTThe protozoan parasiteLeishmania amazonensisis a heme auxotroph and must acquire this essential factor from the environment. Previous studies showed thatL. amazonensisincorporates heme through the transmembrane protein LHR1 (Leishmania HemeResponse 1).LHR1-null promastigotes were not viable, suggesting that the transporter is essential for survival. Here, we compared the growth, differentiation, and infectivity for macrophages and mice of wild-type,LHR1-single-knockout (LHR1/Δlhr1), andLHR1-complemented (LHR1/Δlhr1plusLHR1)L. amazonensisstrains.LHR1/Δlhr1promastigotes replicated poorly in heme-deficient media and had lower intracellular heme content than wild-type parasites.LHR1/Δlhr1promastigotes were also less effective in reducing ferric iron to ferrous iron, a reaction mediated by the heme-containing parasite enzyme LFR1 (Leishmania Ferric Reductase1).LHR1/Δlhr1parasites differentiated normally into aflagellated forms expressing amastigote-specific markers but were not able to replicate intracellularly after infecting macrophages. Importantly, the intracellular growth ofLHR1/Δlhr1amastigotes was fully restored when macrophages were allowed to phagocytose red blood cells prior to infection.LHR1/Δlhr1parasites were also severely defective in the development of cutaneous lesions in mice. All phenotypes observed inLHR1/Δlhr1L. amazonensiswere rescued by expression of episomalLHR1. Our results reveal the importance of efficient heme uptake forL. amazonensisreplication and vertebrate host infectivity, reinforcing the potential usefulness of LHR1 as a target for new antileishmanial drugs.

scholarly journals BrlA and AbaA Govern Virulence-Required Dimorphic Switch, Conidiation, and Pathogenicity in a Fungal Insect Pathogen

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
An-Xue Zhang ◽  
Amina-Zahra Mouhoumed ◽  
Sen-Miao Tong ◽  
Sheng-Hua Ying ◽  
Ming-Guang Feng
Keyword(s):  
Host Tissue ◽  
Asexual Development ◽  
Wild Type ◽  
Developmental Pathway ◽  
Yeast Growth ◽  
Tissue Penetration ◽  
Content Type ◽  
Signaling Systems ◽  
Multiple Signaling

ABSTRACT Dimorphic plant and human mycopathogens require a switch from the usual yeast growth to filamentous growth for host tissue penetration, and the switch is controlled by multiple signaling systems other than the central developmental pathway. Unlike these fungi, dimorphic insect mycopathogens usually grow by hyphal extension, infect the host by hyphal penetration through the insect cuticle, and switch to unicellular blastospores from the penetrating hyphae only after entry into the host hemocoel, where blastospore propagation by yeast-like budding accelerates host mummification. Here, we report a dependence of the virulence-required dimorphic transition on the central pathway activators BrlA and AbaA in Beauveria bassiana. Deletion of brlA or abaA abolished both aerial conidiation and submerged blastospore formation in vitro despite no negative impact on hyphal growth in various media, including a broth mimic of insect hemolymph. The hyphae of either deletion mutant lost insect pathogenicity through normal cuticle penetration, contrasting with a high infectivity of wild-type hyphae. The mutant hyphae injected into the host hemocoel failed to form blastospores, resulting in slower lethal action. Uncovered by transcriptomic analysis, several genes involved in host adhesion and cuticle degradation were sharply repressed in both deletion mutants versus wild type. However, almost all signaling genes homologous to those acting in the dimorphic switch of other fungi were not differentially expressed at a significant level and hence unlikely to be involved in shutting down the dimorphic switch of each deletion mutant. Therefore, like aerial conidiation, the submerged dimorphic switch in vitro and in vivo is a process of asexual development governed by the two central pathway activators in B. bassiana. IMPORTANCE Dimorphic insect mycopathogens infect the host by hyphal penetration through the host cuticle and switch from the penetrating hyphae to unicellular blastospores after entry into the host hemocoel, where blastospore propagation by yeast-like budding accelerates host mummification to death. The fungal virulence-required dimorphic switch is confirmed as a process of asexual development directly regulated by BrlA and AbaA, two key activators of the central developmental pathway in an insect mycopathogen. This finding unveils a novel mechanism distinct from the control of the dimorphic switch by multiple signaling systems other than the central developmental pathway in dimorphic plant and human mycopathogens, which switch from the usual yeast growth to filamentous growth required for pathogenicity through host tissue penetration.

scholarly journals A Glycosylation Mutant of Trypanosoma brucei Links Social Motility Defects In Vitro to Impaired Colonization of Tsetse Flies In Vivo

2015 ◽  
Vol 14 (6) ◽  
pp. 588-592 ◽  
Author(s):  
Simon Imhof ◽  
Xuan Lan Vu ◽  
Peter Bütikofer ◽  
Isabel Roditi
Keyword(s):  
Ectopic Expression ◽  
Signaling Cascades ◽  
Tsetse Flies ◽  
Content Type ◽  
African Trypanosomes ◽  
Social Motility ◽  
Midgut Lumen ◽  
Wild Type Parent

ABSTRACT Transmission of African trypanosomes by tsetse flies requires that the parasites migrate out of the midgut lumen and colonize the ectoperitrophic space. Early procyclic culture forms correspond to trypanosomes in the lumen; on agarose plates they exhibit social motility, migrating en masse as radial projections from an inoculation site. We show that an Rft1 −/− mutant needs to reach a greater threshold number before migration begins, and that it forms fewer projections than its wild-type parent. The mutant is also up to 4 times less efficient at establishing midgut infections. Ectopic expression of Rft1 rescues social motility defects and restores the ability to colonize the fly. These results are consistent with social motility reflecting movement to the ectoperitrophic space, implicate N-glycans in the signaling cascades for migration in vivo and in vitro , and provide the first evidence that parasite-parasite interactions determine the success of transmission by the insect host.

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