scholarly journals Pseudomonas aeruginosa Cytotoxin ExoU Is Injected into Phagocytic Cells during Acute Pneumonia

2010 ◽  
Vol 78 (4) ◽  
pp. 1447-1456 ◽  
Author(s):  
Maureen H. Diaz ◽  
Alan R. Hauser
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune Cells ◽  
Type Iii Secretion ◽  
Cell Types ◽  
Secretion System ◽  
Host Cells ◽  
Phagocytic Cells ◽  
Acute Pneumonia

ABSTRACT ExoU, a cytotoxin translocated into host cells via the type III secretion system of Pseudomonas aeruginosa, is associated with increased mortality and disease severity. We previously showed that impairment of recruited phagocytic cells allowed survival of ExoU-secreting P. aeruginosa in the lung. Here we analyzed types of cells injected with ExoU in vivo using translational fusions of ExoU with a β-lactamase reporter (ExoU-Bla). Cells injected with ExoU-Bla were detectable in vitro but not in vivo, presumably due to the rapid cytotoxicity induced by the toxin. Therefore, we used a noncytotoxic ExoU variant, designated ExoU(S142A)-Bla, to analyze injection in vivo. We determined that phagocytic cells in the lung were frequently injected with ExoU(S142A). Early during infection, resident macrophages constituted the majority of cells into which ExoU was injected, but neutrophils and monocytes became the predominant types of cells into which ExoU was injected upon recruitment into the lung. We observed a modest preference for injection into neutrophils over injection into other cell types, but in general the repertoire of injected immune cells reflected the relative abundance of these cells in the lung. Our results indicate that phagocytic cells in the lung are injected with ExoU and support the hypothesis that ExoU-mediated impairment of phagocytes has a role in the pathogenesis of pneumonia caused by P. aeruginosa.

scholarly journals Role of the Type III Secreted Exoenzymes S, T, and Y in Systemic Spread of Pseudomonas aeruginosa PAO1 In Vivo

2005 ◽  
Vol 73 (3) ◽  
pp. 1706-1713 ◽  
Author(s):  
Russell E. Vance ◽  
Arne Rietsch ◽  
John J. Mekalanos
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Line ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Macrophage Cell ◽  
Type Iii

ABSTRACT Pseudomonas aeruginosa uses a dedicated type III secretion system to deliver toxins directly into the cytoplasm of host cells. While progress has been made in elucidating the function of type III-secreted toxins in vitro, the in vivo functions of the type III-secreted exoenzymes are less well understood, particularly for the sequenced strain PAO1. Therefore, we have systematically deleted the genes for the three known type III effector molecules (exoS, exoT, and exoY) in P. aeruginosa PAO1 and assayed the effect of the deletions, both singly and in combination, on cytotoxicity in vitro and in vivo. We found that the type III secretion system acts differently on different cell types, causing an exoST-dependent rounding of a lung epithelial-like cell line in contrast to causing an exoSTY-independent but translocase (popB)-dependent lysis of a macrophage cell line. We utilized an in vivo competitive infection model to test each of our mutants, examining replication in the lung and spread to secondary sites such as the blood and spleen. Type III mutants inoculated intranasally exhibited only a minor defect in replication and survival in the lung, but popB and exoSTY triple mutants were profoundly defective in their ability to spread systemically. Intravenous injection of the mutants indicated that the type III secretion machinery is required for survival in the blood. Furthermore, our findings suggest that the effector-independent popB-dependent cytotoxicity that we and others have observed in vitro in macrophage cell lines may not be of great importance in vivo.

scholarly journals Impact of Type III Secretion Effectors and of Phenoxyacetamide Inhibitors of Type III Secretion on Abscess Formation in a Mouse Model of Pseudomonas aeruginosa Infection

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Bryan J. Berube ◽  
Katherine R. Murphy ◽  
Matthew C. Torhan ◽  
Nicholas O. Bowlin ◽  
John D. Williams ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Model ◽  
Type Iii Secretion ◽  
Abscess Formation ◽  
Host Cells ◽  
Block Type ◽  
Content Type ◽  
Type Iii

ABSTRACT Pseudomonas aeruginosa is a leading cause of intra-abdominal infections, wound infections, and community-acquired folliculitis, each of which may involve macro- or microabscess formation. The rising incidence of multidrug resistance among P. aeruginosa isolates has increased both the economic burden and the morbidity and mortality associated with P. aeruginosa disease and necessitates a search for novel therapeutics. Previous work from our group detailed novel phenoxyacetamide inhibitors that block type III secretion and injection into host cells in vitro. In this study, we used a mouse model of P. aeruginosa abscess formation to test the in vivo efficacy of these compounds against the P. aeruginosa type III secretion system (T3SS). Bacteria used the T3SS to intoxicate infiltrating neutrophils to establish abscesses. Despite this antagonism, sufficient numbers of functioning neutrophils remained for proper containment of the abscesses, as neutrophil depletion resulted in an increased abscess size, the formation of dermonecrotic lesions on the skin, and the dissemination of P. aeruginosa to internal organs. Consistent with the specificity of the T3SS-neutrophil interaction, P. aeruginosa bacteria lacking a functional T3SS were fully capable of causing abscesses in a neutropenic host. Phenoxyacetamide inhibitors attenuated abscess formation and aided in the immune clearance of the bacteria. Finally, a P. aeruginosa strain resistant to the phenoxyacetamide compound was fully capable of causing abscess formation even in the presence of the T3SS inhibitors. Together, our results further define the role of type III secretion in murine abscess formation and demonstrate the in vivo efficacy of phenoxyacetamide inhibitors in P. aeruginosa infection.

scholarly journals An in vivo inducible gene of Pseudomonas aeruginosa encodes an anti-ExsA to suppress the type III secretion system

2004 ◽  
Vol 54 (2) ◽  
pp. 307-320 ◽  
Author(s):  
Un-Hwan Ha ◽  
Jaewha Kim ◽  
Hassan Badrane ◽  
Jinghua Jia ◽  
Henry V. Baker ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Inducible Gene

scholarly journals Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne-Gaëlle Leroy ◽  
Jocelyne Caillon ◽  
Nathalie Caroff ◽  
Alexis Broquet ◽  
Stéphane Corvec ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Trials ◽  
Respiratory Infections ◽  
Direct Interaction ◽  
Membered Ring ◽  
Careful Examination ◽  
Major Interest ◽  
Acute Pneumonia

Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, including Pseudomonas aeruginosa (PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlighted in vitro, these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.

scholarly journals Διερεύνηση αντιμικροβιακής αντοχής και παθογονικότητας νοσοκομεικακών στελεχών ψευδομονάδων

2015 ◽  
Author(s):  
Όλγα Οικονόμου
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Galleria Mellonella ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Maldi Tof Ms ◽  
Type Iii ◽  
Maldi Tof ◽  
Tof Ms

Οι ψευδομονάδες είναι αζυμωτικά Gram αρνητικά βακτηρίδια, αυστηρά αερόβια και οξειδάση θετικά. Η Pseudomonas aeruginosa αποτελεί κυρίως αίτιο σοβαρών και ποικίλων νοσοκομειακών λοιμώξεων αλλά και λοιμώξεων της κοινότητας, οι οποίες συνήθως είναι ηπιότερες. Την τελευταία δεκαετία έχει παρατηρηθεί μεγάλη αύξηση των ανθεκτικών στις καρβαπενέμες στελεχών Pseudomonas aeruginosa, γεγονός που αποτελεί σημαντικό πρόβλημα στην αντιμετώπιση αυτών των λοιμώξεων, καθώς οι θεραπευτικές επιλογές που απομένουν είναι ελάχιστες. Ο κυριότερος μηχανισμός αντοχής είναι η παραγωγή καρβαπενεμασών, ενζύμων δηλαδή που υδρολύουν τις καρβαπενέμες.Σκοπός της εργασίας μας ήταν α) η φαινοτυπική και μοριακή ανίχνευση των μεταλλο-β-λακταμασών ως επίκτητου μηχανισμού αντοχής στις καρβαπενέμες πολυανθεκτικών στελεχών P. aeruginosa β) η μελέτη του γενετικού περιβάλλοντος των γονιδίων που κωδικοποιούν καρβαπενεμάση και ο χαρακτηρισμός των ιντεγκρονίων, γ) η μοριακή τυποποίηση των στελεχών αυτών και δ) η μελέτη της παθογονικότητας των επικρατούντων κλώνων.Για το λόγο αυτό μελετήσαμε 387 στελέχη από το Πανεπιστημιακό Νοσοκομείο της Λάρισας και από το Νοσοκομείο «Η Σωτηρία» της Αθήνας από τα οποία τα 126 βρέθηκαν θετικά στην παραγωγή καρβαπενεμάσης τόσο φαινοτυπικά όσο και μοριακά. Συγκεκριμένα, έγινε φαινοτυπική ανίχνευση της παραγωγής καρβαπενεμασών με διάφορες μεθόδους όπως και προσδιορισμός των γονιδίων που είναι υπεύθυνα για την παραγωγή τους με μοριακές μεθόδους, ενώ παράλληλα μελετήθηκε και το γενετικό τους περιβάλλον. Ακολούθησε τυποποίηση των εν λόγω στελεχών με MLST και σύγκριση των κλώνων στα δύο νοσοκομεία. Επιπλέον, μελετήθηκε η παθογονικότητα των επικρατέστερων κλώνων, με πειράματα in vivo. Κατά το χρονικό διάστημα από τον Μάρτιο έως και τον Οκτώβριο του 2011 απομονώθηκαν συνολικά 813 στελέχη Pseudomonas aeruginosa εκ των οποίων 387 (47,6%) παρουσίασαν αντοχή στις καρβαπενέμες (MIC>8μg/ml) σύμφωνα με τα κριτήρια του CLSI, 2012. Από τα 387 ανθεκτικά στις καρβαπενέμες στελέχη, 126 (32,5%) βρέθηκαν θετικά με τις διάφορες φαινοτυπικές δοκιμασίες δηλώνοντας την παρουσία μέταλλο-β-λακταμάσης (τάξης Β) ενώ ανιχνεύτηκαν διάφορα αλληλόμορφα γονίδια της καρβαπενεμάσης VIM. Η ανάλυση της νουκλεοτιδικής αλληλουχίας του γονιδίου blaVIM, που ακολούθησε, κατέδειξε ότι από τα 126 στελέχη, τα 80 έφεραν το αλληλόμορφο blaVIM-2, τα 36 το αλληλόμορφο blaVIM-4, τα 9 το αλληλόμορφο blaVIM-1και σε 1 στέλεχος το αλληλόμορφο blaVIM-17.Σε όλα τα στελέχη το γονίδιο blaVIM βρέθηκε να αποτελεί τμήμα της γονιδιακής συστοιχίας ιντεγκρονίων τάξης 1, γενετικών δομών που έχουν συσχετιστεί με την εμφάνιση πολυανθεκτικού φαινοτύπου, καθώς είναι ικανές να συσσωρεύουν γονίδια ανθεκτικότητας έναντι διαφόρων τάξεων αντιβιοτικών. Στη συνέχεια η τυποποίηση των ανθεκτικών στις καρβαπενέμες στελεχών P. aeruginosa που διενεργήθηκε με τη μέθοδο MLST, ανέδειξε ότι τα στελέχη P. aeruginosa άνηκαν σε 9 διαφορετικούς STs τύπους και συγκεκριμένα στους ST-111, ST-235, ST-244, ST-253, ST-277, ST-308, ST-395, ST-773 και ST-1457.Η μελέτη της παθογονικότητας αντιπροσωπευτικών MLST στελεχών P. aeruginosa πραγματοποιήθηκε στο μη σπονδυλωτό μοντέλο Galleria mellonella. H Galleria mellonella αποτελεί ένα κατάλληλο μη θηλαστικό μοντέλο-ξενιστή για τη μελέτη του ρόλου του Type III Secretion System στη παθογένεση των ψευδομονάδων. Όλα τα στελέχη αναδείχθηκαν θετικά για τα γονίδια exoT και exoY ενώ διαφορές υπήρχαν στα γονίδια exoS και exoU. Τα υπό μελέτη στελέχη εμφάνισαν διαφορές στη παθογονικότητα. Συγκεκριμένα οι κλώνοι ST111 και ST235 οι οποίοι επικρατούν, αναδείχθηκαν οι λιγότερο παθογονικοί με ποσοστό επιβίωσης των προνυμφών μεγαλύτερο του 50% το πρώτο 24ωρο ενώ οι ST277, ST244 και ST773 αναδείχθηκαν οι πιο παθογονικοί με ποσοστό επιβίωσης 0% στις πρώτες 24 ώρες, παρόμοιο με αυτό των πρότυπων στελεχών.Συνοψίζοντας, καταλήγουμε στα παρακάτω συμπεράσματα:1.Το ποσοστό των ανθεκτικών στις καρβαπενέμες στελεχών P. aeruginosa στα ελληνικά νοσοκομεία για το χρονικό διάστημα που εξετάσαμε ήταν πολύ υψηλό (47,6%), ενώ παράλληλα εμφάνιζαν πολυανθεκτικούς φαινοτύπους, περιορίζοντας τις θεραπευτικές επιλογές2.Η ανθεκτικότητα στις καρβαπενέμες των στελεχών P. aeruginosa οφείλεται σε αρκετά μεγάλο ποσοστό (32,5%) στην παρουσία των αλληλομόρφων του γονιδίου VIM (VIM-1, VIM-2, VIM-4 και VIM-17), τα οποία διαπιστώθηκε ότι εδράζονται επί ιντεγκρονίων, γενετικών δομών με ικανότητα ενσωμάτωσης και άλλων γονιδίων που προσδίδουν αντοχή και σε άλλες τάξεις αντιβιοτικών.3.Η πλειονότητα των ανθεκτικών στις καρβαπενέμες στελεχών P. aeruginosa άνηκαν στους ST-111MLST και ST-235MLST4.Αποτελεί επιτακτική ανάγκη η εύρεση μεθόδων για την άμεση ανίχνευση των στελεχών που παράγουν καρβαπενεμάσες έτσι ώστε να εμποδίζεται η διασπορά. Ανάμεσα στις μεθόδους ανίχνευσης, η τροποποιημένη MALDI-TOF MS αποτελεί μία μέθοδο με υψηλή ευαισθησία και ειδικότητα στην ανίχνευση των ψευδομονάδων που παράγουν καρβαπενεμάση ενώ η δοκιμασία Blue-Carba αποτελεί μια φτηνή, γρήγορη και αξιόπιστη μέθοδο για την ανίχνευση των ψευδομονάδων που παράγουν καρβαπενεμάσες, που θα μπορούσε να εφαρμοσθεί σε οποιοδήποτε εργαστήριο χωρίς ιδιαίτερο εξοπλισμό.5.Υπάρχουν διαφορές στην παθογονικότητα των στελεχών που ανήκουν σε διαφορετικούς STs που δε σχετίζονται με την παρουσία συγκεκριμένων γονιδίων παθογονικότητας του εκκριτικού συστήματος τύπου ΙΙΙ. Οι πιο συχνοί MLST τύποι φαίνεται να σχετίζονται με μειωμένη παθογονικότητα εύρημα που πιθανότατα συσχετίζεται με την ικανότητα τους να διασπείρονται και να επικρατούν έναντι των υπολοίπων.

scholarly journals Salmonella-Induced Caspase-2 Activation in Macrophages

2000 ◽  
Vol 192 (7) ◽  
pp. 1035-1046 ◽  
Author(s):  
Veronika Jesenberger ◽  
Katarzyna J. Procyk ◽  
Junying Yuan ◽  
Siegfried Reipert ◽  
Manuela Baccarini
Keyword(s):  
Type Iii Secretion ◽  
Caspase 3 ◽  
Secretion System ◽  
Caspase 1 ◽  
Chemical Inhibition ◽  
Induction Of Apoptosis ◽  
Caspase 2 ◽  
Induced Apoptosis

The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and in vivo. These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host's apoptotic machinery by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. We show that caspase-1–deficient macrophages undergo apoptosis within 4–6 h of infection with invasive bacteria. This process requires SipB, implying that this protein can initiate the apoptotic machinery by regulating components distinct from caspase-1. Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. Besides caspase-2, the caspase-1–independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of which occurs during caspase-1–dependent apoptosis. By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1–dependent and –independent apoptosis. Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. The ability of Salmonella to induce caspase-1–independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis.

scholarly journals Pseudomonas aeruginosa injects NDK into host cells through a type III secretion system

Microbiology ◽  
2014 ◽  
Vol 160 (7) ◽  
pp. 1417-1426 ◽  
Author(s):  
Dennis Neeld ◽  
Yongxin Jin ◽  
Candace Bichsel ◽  
Jinghua Jia ◽  
Jianhui Guo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Mammalian Host ◽  
Type I ◽  
Dependent Manner ◽  
Type Iii

Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen possessing a type III secretion system (T3SS) which injects toxic effector proteins into mammalian host cells. In previous studies, P. aeruginosa strains lacking all of the known type III effectors were shown to cause cytotoxicity upon prolonged infection time. In this study, we report the identification of a new cytotoxin, nucleoside diphosphate kinase (NDK), which is injected into eukaryotic cells in a T3SS-dependent manner. Injection of NDK is inhibited by the presence of previously known effectors of the T3SS, with an effectorless strain injecting the highest amount, suggesting active competition with the known T3SS effectors. NDK is shown to cause a cytotoxic response when expressed in eukaryotic cells, and P. aeruginosa strains harbouring NDK also show a greater toxicity than strains lacking it. Interestingly, the cytotoxic effect of intracellular NDK is independent of its kinase activity. In previous studies, NDK was shown to be secreted into culture supernatants via a type I secretion system and cause cytotoxicity in a kinase-dependent manner. Therefore, the current study highlights an alternative route of NDK secretion as well as two different cytotoxic mechanisms of NDK, depending on the extra- or intra-cellular location of the protein.

scholarly journals Differential ASC requirements reveal a key role for neutrophils and a noncanonical IL-1β response to Pseudomonas aeruginosa

2015 ◽  
Vol 309 (8) ◽  
pp. L902-L913 ◽  
Author(s):  
Yash R. Patankar ◽  
Rodwell Mabaera ◽  
Brent Berwin
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Infection ◽  
Adaptor Protein ◽  
Ocular Infection ◽  
Lethal Challenge ◽  
Type Three Secretion System ◽  
Acute Pneumonia ◽  
Marked Deficit

The NLRC4 inflammasome is responsible for IL-1β processing by macrophages in response to Pseudomonas aeruginosa infection. We therefore hypothesized that mice that lack ASC, an NLRC4 inflammasome adaptor protein necessary for in vitro IL-1β production by macrophages, would be preferentially protected from a hyperinflammatory lethal challenge that is dependent on bacterial type three secretion system (T3SS) activity. We report herein that lack of ASC does not confer preferential protection in response to P. aeruginosa acute infection and that ASC−/− mice are capable of producing robust amounts of IL-1β comparable with C57BL/6 mice. We now identify that neutrophils represent the ASC-independent source of IL-1β production during the acute phases of infection both in models of acute pneumonia and peritonitis. Consequently, depletion of neutrophils in ASC−/− mice leads to a marked deficit in IL-1β production in vivo. The pulmonary neutrophil IL-1β response is predominantly dependent on caspase-1, which contrasts with data derived from ocular infection. These studies therefore identify a noncanonical mechanism of IL-1β production by neutrophils independent of ASC and demonstrate the first physiological contribution of neutrophils as an important source of IL-1β in response to acute P. aeruginosa infection during acute pneumonia and peritonitis.

scholarly journals RNase E Promotes Expression of Type III Secretion System Genes in Pseudomonas aeruginosa

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Josh S. Sharp ◽  
Arne Rietsch ◽  
Simon L. Dove
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Rnase E ◽  
Content Type ◽  
Type Iii ◽  
Small Regulatory Rnas

ABSTRACT Pseudomonas aeruginosa is an important opportunistic pathogen that employs a type III secretion system (T3SS) to inject effector proteins into host cells. Using a protein depletion system, we show that the endoribonuclease RNase E positively regulates expression of the T3SS genes. We also present evidence that RNase E antagonizes the expression of genes of the type VI secretion system and limits biofilm production in P. aeruginosa. Thus, RNase E, which is thought to be the principal endoribonuclease involved in the initiation of RNA degradation in P. aeruginosa, plays a key role in controlling the production of factors involved in both acute and chronic stages of infection. Although the posttranscriptional regulator RsmA is also known to positively regulate expression of the T3SS genes, we find that RNase E does not appreciably influence the abundance of RsmA in P. aeruginosa. Moreover, we show that RNase E still exerts its effects on T3SS gene expression in cells lacking all four of the key small regulatory RNAs that function by sequestering RsmA. IMPORTANCE The type III secretion system (T3SS) is a protein complex produced by many Gram-negative pathogens. It is capable of injecting effector proteins into host cells that can manipulate cell metabolism and have toxic effects. Understanding how the T3SS is regulated is important in understanding the pathogenesis of bacteria with such systems. Here, we show that RNase E, which is typically thought of as a global regulator of RNA stability, plays a role in regulating the T3SS in Pseudomonas aeruginosa. Depleting RNase E results in the loss of T3SS gene expression as well as a concomitant increase in biofilm formation. These observations are reminiscent of the phenotypes associated with the loss of activity of the posttranscriptional regulator RsmA. However, RNase E-mediated regulation of these systems does not involve changes in the abundance of RsmA and is independent of the known small regulatory RNAs that modulate RsmA activity.

scholarly journals Interactions between effector proteins of the Pseudomonas aeruginosa type III secretion system do not significantly affect several measures of disease severity in mammals

Microbiology ◽  
2006 ◽  
Vol 152 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Ciara M. Shaver ◽  
Alan R. Hauser
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Disease Severity ◽  
Type Iii Secretion ◽  
Disease Process ◽  
Effector Proteins ◽  
Host Cells ◽  
Secreted Proteins ◽  
Secretion Systems ◽  
Type Iii

The effector proteins of the type III secretion systems of many bacterial pathogens act in a coordinated manner to subvert host cells and facilitate the development and progression of disease. It is unclear whether interactions between the type-III-secreted proteins of Pseudomonas aeruginosa result in similar effects on the disease process. We have previously characterized the contributions to pathogenesis of the type-III-secreted proteins ExoS, ExoT and ExoU when secreted individually. In this study, we extend our prior work to determine whether these proteins have greater than expected effects on virulence when secreted in combination. In vitro cytotoxicity and anti-internalization activities were not enhanced when effector proteins were secreted in combinations rather than alone. Likewise in a mouse model of pneumonia, bacterial burden in the lungs, dissemination and mortality attributable to ExoS, ExoT and ExoU were not synergistically increased when combinations of these effector proteins were secreted. Because of the absence of an appreciable synergistic increase in virulence when multiple effector proteins were secreted in combination, we conclude that any cooperation between ExoS, ExoT and ExoU does not translate into a synergistically significant enhancement of disease severity as measured by these assays.

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