Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

Abstract

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

Achromobacter xylosoxidans and Stenotrophomonas maltophilia: Emerging Pathogens Well-Armed for Life in the Cystic Fibrosis Patients’ Lung

“…Well-characterized in P. aeruginosa , only a few works have investigated hypermutation in Axc [ 35 , 36 , 37 ] and Sm [ 38 , 39 , 40 , 41 ]. These studies found strains that undergo mutations at a high rate (mutation frequency ≥ 4.0 × 10 −7 ) in both Axc and Sm CF populations and considered hypermutation as a key adaptive pathway of both pathogens.…”

“…Being hypermutable can confer a transient advantage to fluctuating environmental conditions, but mutation status usually evolves over time to a less mutator phenotype due to fitness cost associated with hypermutation [ 39 , 41 ]. However, studies have reported CF patients with successively recovered isolates displaying increased mutation frequencies during persistence [ 38 , 40 , 42 ], suggesting that the dynamics of hypermutators also depend on specific conditions linked to the host/strain partnership and that the fitness cost of hypermutable Sm strains may not systematically impede long-standing CF lung infection.…”

“…The genomes of Axc and Sm are highly dynamic, and numerous alterations in the genomic content of Axc and Sm , named microevolution, have been demonstrated during their persistence in the CF lung, as previously studied in P. aeruginosa [ 43 , 44 ]. During Acx or Sm persistence, studies based on pulsed-field gel electrophoresis (PFGE) first led to the recognition of “true” chronic colonization as well as intra-clonal evolution of PFGE profiles over time through genome rearrangements [ 15 , 39 , 40 , 41 , 42 , 45 ]. As for P. aeruginosa , microevolution was related to lung habitat pathoadaptation by the authors.…”

“…Regarding Axc , a strong decrease in the expression of genes coding for T3SS and motility [ 78 ], as well as mutations in virulence-associated genes [ 46 ], have also been observed for strains involved in late infection episodes compared with strains involved in early infections from the same patient. For Sm , a lower motility, a decrease or the loss of some virulence factors, and decreased virulence both in human cells and in an invertebrate model have been demonstrated [ 41 , 42 ]. All these observations underline that both Axc and Sm have the capacity to modulate their pathogenicity over time.…”

The epidemiology of Stenotrophomonas maltophilia and Achromobacter xylosoxidans infections

“…4 , 5 In this nested case-control trial, we explored the epidemiology of 66 S. maltophilia infections and of 8 A. xylosoxidans infections, for a 12-year period (2011–2022). In order to avoid classification bias and the inclusion of asymptomatic carriers as cases, 8 , 9 only patients with BSI (per established definition 7 , 10 ) were enrolled as cases. The incidences of S. maltophilia infections and of A. xylosoxidans infections, had not increased at SMC during the study.…”