Influence of Virulence Genotype and Resistance Profile in the Mortality of Pseudomonas aeruginosa Bloodstream Infections

Peña, Carmen; Cabot, Gabriel; Gómez-Zorrilla, Sílvia; Zamorano, Laura; Ocampo-Sosa, Alain A.; Murillas, Javier; Almirante, Benito; Pomar, Virginia; Aguilar, Manuela; Granados, A.L. Ortega; Calbo, Esther; Rodríguez‐Baño, Jesús; Rodríguez-López, Fernando; Tubau, Fé; Martı́nez-Martı́nez, Luis; Oliver, Antonio; Gurguí, Mercé; Sordé, Roger; Larrosa, Nieves; Martin, Charlene; Fontanals, Dionísia; Cueto, Marina de; Navarro, Marian; Torre-Cisneros, J; Casal, Manuel Crespo; Lara, Rosario; Nátera, Clara; Rivero-Santana, Amado

doi:10.1093/cid/ciu866

Cited by 168 publications

(206 citation statements)

References 38 publications

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“…In addition, previous studies were shown that the presence of the TTSS effector genotypes, especially exoU genotype, correlate with increasing the virulence and resistance to one or more antibiotics. In a study by Agnello et al, they were found that the presence of exoU gene was significantly correlated with flouroquinolones-resistance (4 (23,26). In present study 81.7% and 88.6% of isolates were resistant to ciprofloxacin and levofloxacin; respectively.…”

Section: Discussionsupporting

confidence: 53%

Detection of Exotoxins and Antimicrobial Susceptibility Pattern in Clinical Pseudomonas Aeruginosa Isolates

Mohamad¹,

Rostami²,

Zamanzad³

et al. 2017

Avicenna J Clin Microb Infec

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Section: Discussionsupporting

confidence: 53%

Detection of Exotoxins and Antimicrobial Susceptibility Pattern in Clinical Pseudomonas Aeruginosa Isolates

Mohamad¹,

Rostami²,

Zamanzad³

et al. 2017

Avicenna J Clin Microb Infec

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“…Fourteen P. aeruginosa ST175 isolates recovered from patients with bloodstream infections in a 2008 -2009 multicenter study in Spain were studied (18,22). The isolates selected included as many as 2 ST175 representatives for each of the 10 hospitals participating in the multicenter study.…”

Section: Methodsmentioning

confidence: 99%

Deciphering the Resistome of the Widespread Pseudomonas aeruginosa Sequence Type 175 International High-Risk Clone through Whole-Genome Sequencing

Cabot

López-Causapé

Ocampo-Sosa

et al. 2016

Antimicrob Agents Chemother

104

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g Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones.

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“…The present data, together with the results obtained previously with INP1855 (35), strongly suggest an advantage for hydroxyquinolines over salicylidene acylhydrazides. Hydroxyquinolines, indeed, show better effects on both iT3SS and the fT3SS, two key determinants in the pathogenicity of P. aeruginosa (3,11,12,27,55).…”

Section: Discussionmentioning

confidence: 91%

“…ncreasing resistance of clinical isolates of Pseudomonas aeruginosa to current recommended antipseudomonal antibiotics is associated with poor clinical outcome and increased mortality (1)(2)(3), prompting the search for innovative therapeutic strategies. However, very few novel antipseudomonal agents are currently under development (4).…”

mentioning

confidence: 99%

“…iT3SS expression is associated with poor clinical outcomes and high morbidity in acute infections (3,11,12). The system consists in a syringe-like machine injecting bacterial effector proteins from the bacterial cytosol directly into the host cell by the concerted action of a secretion apparatus (comprising among others the protein PscF forming the needle filament) and a translocon (proteins PopB, PopD, and PcrV; see Fig.…”

mentioning

confidence: 99%

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Salicylidene Acylhydrazides and Hydroxyquinolines Act as Inhibitors of Type Three Secretion Systems in Pseudomonas aeruginosa by Distinct Mechanisms

Anantharajah

Buyck

Sundin³

et al. 2017

Antimicrob Agents Chemother

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Type 3 secretion systems (T3SSs) are major virulence factors in Gramnegative bacteria. Pseudomonas aeruginosa expresses two T3SSs, namely, an injectisome (iT3SS) translocating effector proteins in the host cell cytosol and a flagellum (fT3SS) ensuring bacterial motility. Inhibiting these systems is an appealing therapeutic strategy for acute infections. This study examines the protective effects of the salicylidene acylhydrazide INP0341 and of the hydroxyquinoline INP1750 (previously described as T3SS inhibitors in other species) toward cytotoxic effects of P. aeruginosa in vitro. Both compounds reduced cell necrosis and inflammasome activation induced by reference strains or clinical isolates expressing T3SS toxins or only the translocation apparatus. INP0341 inhibited iT3SS transcriptional activation, including in strains with constitutive iT3SS expression, and reduced the total expression of toxins, suggesting it targets iT3SS gene transcription. INP1750 inhibited toxin secretion and flagellar motility and impaired the activity of the YscN ATPase from Yersinia pseudotuberculosis (homologous to the ATPase present in the basal body of P. aeruginosa iT3SS and fT3SS), suggesting that it rather targets a T3SS core constituent with high homology among iT3SS and fT3SS. This mode of action is similar to that previously described for INP1855, another hydroxyquinoline, against P. aeruginosa. Thus, although acting by different mechanisms, INP0341 and INP1750 appear as useful inhibitors of the virulence of P. aeruginosa. Hydroxyquinolines may have a broader spectrum of activity by the fact they act upon two virulence factors (iT3SS and fT3SS).

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Influence of Virulence Genotype and Resistance Profile in the Mortality of Pseudomonas aeruginosa Bloodstream Infections

Abstract: Our results indicate that the exoU genotype, which is associated with specific susceptibility profiles, is a relevant independent marker of early mortality in P. aeruginosa bacteremia.

Cited by 168 publications

References 38 publications

Detection of Exotoxins and Antimicrobial Susceptibility Pattern in Clinical Pseudomonas Aeruginosa Isolates

Detection of Exotoxins and Antimicrobial Susceptibility Pattern in Clinical Pseudomonas Aeruginosa Isolates

Deciphering the Resistome of the Widespread Pseudomonas aeruginosa Sequence Type 175 International High-Risk Clone through Whole-Genome Sequencing

Salicylidene Acylhydrazides and Hydroxyquinolines Act as Inhibitors of Type Three Secretion Systems in Pseudomonas aeruginosa by Distinct Mechanisms

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