Pseudomonas aeruginosa Type III Secretion System Virulotypes and Their Association with Clinical Features of Cystic Fibrosis Patients

Abstract

Purpose Pseudomonas aeruginosa appears as the main pathogen in cystic fibrosis (CF) involved in recurrent pneumonia and pulmonary exacerbations. The type III secretion system (T3SS) is one of its main determinants of virulence and is associated with poor clinical progression and increased mortality. This study determined the relationship of clinical features of patients with CF and P. aeruginosa T3SS virulotypes. Materials and Methods From January 2018 to March 2019, P. aeruginosa were isolated from sputum and/or oropharyngeal swabs. T3SS markers ( exoS, exoU, exoT and exoY ) were detected by PCR. Clinical severity according to Shwachman-Kulckycki score and spirometry data were associated with T3SS virulotypes. Results A total of 49 patients had positive cultures for P. aeruginosa . T3SS virulence-related markers were detected as follows: exoS 97.9% (n=48), exoU 63.2% (n=31), exoT 95.9% (n=47) and exoY 97.9% (n=48). The prevalence of exoS + /exoU + virulotype was higher than previously reported in CF settings, being detected in 61.2% of the evaluated isolates, present in 70% of intermittent infections and with a significantly higher frequency in cases of exacerbations. The presence of exoU in chronic infection was not associated with poor clinical results. In chronic infections, the exoS + /exoU − virulotype prevailed (77.8%) and was associated to worse clinical results according to the Shwachman-Kulckycki score and spirometric. Conclusion Our findings revealed a high prevalence of the atypical exoS + /exoU + virulotype among P. aeruginosa isolates from patients with CF, which was associated with intermittent infection and early clinical alterations, while the exoS + /exoU − virulotype was associated with chronic infection and worse clinical results. Finally, the presented data highlight the relevance of T3SS virulence markers in the clinical progression and disease severity in CF patients.

Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors

“…ExoS, whose production was recently associated with chronic infections and worse clinical outcomes in CF patients [ 128 ] is found in 58–72% of the clinical isolates [ 113 ] and possesses the same bifunctional activity as ExoT [ 117 ]. Its GAP activity is directed towards the same three GTPases, but unlike ExoT, the ADPRT domain of ExoS targets a wide range of cell factors and pathways, thereby producing several adverse effects on the host cells, such as cell death, actin cytoskeletal disruption, inhibition of DNA synthesis, vesicular trafficking, or endocytosis [ 117 ].…”

From genotype to phenotype: adaptations of Pseudomonas aeruginosa to the cystic fibrosis environment

“…In connection with this, CF isolates from chronic infection strains often lacks the PAPI-2 encoded cytotoxin ExoU. They instead harbour the type III secretion system (T3SS) effector ExoS, which is chromosomally encoded and has less virulent properties than ExoU [142][143][144][145]. However, mutations in major virulence and quorum-sensing (QS) regulators, such as retS, exsA or lasR, are the main perpetrators of the lowvirulence state of chronic P. aeruginosa (Fig.…”

Genomic Analysis of Carbapenem-Resistant Pseudomonas aeruginosa Isolated From Urban Rivers Confirms Spread of Clone Sequence Type 277 Carrying Broad Resistome and Virulome Beyond the Hospital

“…Pseudomonas aeruginosa is known to have five TSSs, of which Types I (T1SS), II (T2SS), and III (T3SS) are involved in the virulence of this pathogen. Several studies have linked these TSSs with poor outcomes of patients with acute respiratory diseases (i.e., pneumonia), with T3SS being one of the most clinically relevant virulence determinants (Hauser, 2011;McMackin et al, 2019;Sarges et al, 2020). In this context, we detected ExoTSY exotoxins-encoding genes in both clinical and environmental strains.…”

“…In this context, we detected ExoTSY exotoxins-encoding genes in both clinical and environmental strains. ExoTSY exotoxins are secreted by T3SS and reported to be involved in lung injury, pulmonaryvascular barrier disruption, and end-organ dysfunction in chronic infections, mainly in CF patients; as well as with mortality in animal models (Lu et al, 2014;Sarges et al, 2020;Jurado-Martín et al, 2021). Interestingly, the toxA gene (exotoxin A), which is present in the most clinically P. aeruginosa strains (Khosravi et al, 2016) was also identified in environmental strains.…”