Gene flow, recombination, and positive selection in Stenotrophomonas maltophilia: mechanisms underlying the diversity of the widespread opportunistic pathogen

Genome ◽  
2016 ◽  
Vol 59 (12) ◽  
pp. 1063-1075 ◽  
Author(s):  
Dong Yu ◽  
Zhiqiu Yin ◽  
Beiping Li ◽  
Yuan Jin ◽  
Hongguang Ren ◽  
...  

Stenotrophomonas maltophilia is a global multidrug-resistant human opportunistic pathogen in clinical environments. Stenotrophomonas maltophilia is also ubiquitous in aqueous environments, soil, and plants. Various molecular typing methods have revealed that S. maltophilia exhibits high levels of phenotypic and genotypic diversity. However, information regarding the genomic diversity within S. maltophilia and the corresponding genetic mechanisms resulting in said diversity remain scarce. The genome sequences of 17 S. maltophilia strains were selected to investigate the mechanisms contributing to genetic diversity at the genome level. The core and large pan-genomes of the species were first estimated, resulting in a large, open pan-genome. A species phylogeny was also reconstructed based on 344 orthologous genes with one copy per genome, and the contribution of four evolutionary mechanisms to the species genome diversity was quantified: 15%–35% of the genes showed evidence for recombination, 0%–25% of the genes in one genome were likely gained, 0%–44% of the genes in some genomes were likely lost, and less than 0.3% of the genes in a genome were under positive selection pressures. We observed that, among the four main mechanisms, homologous recombination plays a key role in maintaining diversity in S. maltophilia. In this study, we provide an overview of evolution in S. maltophilia to provide a better understanding of its evolutionary dynamics and its relationship with genome diversity.

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Maria F. Mojica ◽  
Krisztina M. Papp-Wallace ◽  
Magdalena A. Taracila ◽  
Melissa D. Barnes ◽  
Joseph D. Rutter ◽  
...  

ABSTRACT Stenotrophomonas maltophilia is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for S. maltophilia is urgent. We demonstrate the in vitro efficacy of aztreonam-avibactam (ATM-AVI) against S. maltophilia and kinetically characterize the inhibition of the L2 β-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of S. maltophilia, addressing an unmet medical need.


2019 ◽  
Author(s):  
Matthias I Gröschel ◽  
Conor J Meehan ◽  
Ivan Barilar ◽  
Margo Diricks ◽  
Aitor Gonzaga ◽  
...  

AbstractRecent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analysed an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harboured strains of all degrees of human virulence. Lineage Sm6 comprised the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identified potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.One Sentence SummaryThe S. maltophilia complex comprises genetically diverse, globally distributed lineages with evidence for intra-hospital transmission.


2016 ◽  
Vol 60 (9) ◽  
pp. 5130-5134 ◽  
Author(s):  
Maria F. Mojica ◽  
Christopher P. Ouellette ◽  
Amy Leber ◽  
M. Brian Becknell ◽  
Monica I. Ardura ◽  
...  

ABSTRACTStenotrophomonas maltophiliais an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-β-lactamase-producingS. maltophiliarefractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient'sS. maltophiliaisolate.


2020 ◽  
Author(s):  
Mirja Gudzuhn ◽  
Ifey Alio ◽  
Jörg Steinmann ◽  
Nina Schützenmeister ◽  
Wolfgang R. Streit

<p><em>Stenotrophomonas maltophilia</em> is a multidrug resistant human nosocomial opportunistic pathogen. It contributes to disease progression in cystic fibrosis patients and is found in wounds, other infected tissues and on catheter surfaces. <em>S. maltophilia</em> is globally distributed and forms 23 distinct phylogenetic clusters (1, 2). Due to its multidrug resistance, it is extremely difficult to heal <em>S. maltophilia</em> caused infections. Colistin is a last-resort antibiotic against multidrug resistant pathogens. However, this study reveals that the minimal inhibitory concentration (MIC) of colistin varies strongly between 22 tested clinical isolates by ranging from 6.25 - >100 µg/ml. The minimal biofilm inhibitory concentration (MBIC) was detected to be much higher. On 41% of the isolates, colistin proved to be very effective on planktonic cells (MIC-value ≤6.25 µg/ml), but less effective on biofilm cells represented by only 18% of the isolates (MBIC-value <100 µg/ml). Thus, we screened for substances, which prevented specifically the biofilm formation or were involved in the removal of established biofilms. We identified several natural fungal compounds and synthetically produced analogues that affect the biofilm of <em>S. maltophilia</em>. In microtiter plate assays, the three substances HH-R6, HH-R8 and HH-R9, which belong to the rubrolides, had with 63 - 83 % the strongest biofilm reduction effect on the biofilm of <em>S. maltophilia</em> K279a. However, microscopy of the biofilms still revealed some living adhered cells although the biofilm structure was strongly impaired. Furthermore, the antibiofilm effect and the impact on the biofilm structure varied strongly among different clinical <em>S. maltophilia</em> isolates. Ongoing transcriptome analyses are expected to shed light on the biofilm inhibiting mechanism of these substances and to get further evidences how they can be used in a clinical setting in the future.</p> <p> </p> <p>1   Steinmann J., Mamat U., Abda E.M., <em>et al</em>. Analysis of Phylogenetic Variation of <em>Stenotrophomonas maltophilia</em> Reveals Human-Specific Branches. Front Microbiol. 2018, 9:806 (2018). doi:10.3389/fmicb.2018.00806</p> <p>2   Gröschel, M.I., Meehan, C.J., Barilar, I. <em>et al</em>. The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist <em>Stenotrophomonas maltophilia</em>. Nat Commun 11, 2044 (2020). https://doi.org/10.1038/s41467-020-15123-0</p>


2013 ◽  
Vol 79 (18) ◽  
pp. 5593-5600 ◽  
Author(s):  
Jian Liu ◽  
Peng Chen ◽  
Congyi Zheng ◽  
Yu-Ping Huang

ABSTRACTStenotrophomonas maltophiliais an important global opportunistic pathogen for which limited therapeutics are available because of the emergence of multidrug-resistant strains. A novel bacteriocin, maltocin P28, which is produced byS. maltophiliastrain P28, may be the first identified phage tail-like bacteriocin fromS. maltophilia. Maltocin P28 resembles a contractile but nonflexible phage tail structure based on electron microscopy, and it is sensitive to trypsin, proteinase K, and heat. SDS-PAGE analysis of maltocin P28 revealed two major protein bands of approximately 43 and 20 kDa. The N-terminal amino acid residues of these two major subunits were sequenced, and the maltocin P28 gene cluster was located on theS. maltophiliaP28 chromosome. Our sequence analysis results indicate that this maltocin gene cluster consists of 23 open reading frames (ORFs), and that its gene organization is similar to that of the P2 phage genome and R2 pyocin gene cluster. ORF17 and ORF18 encode the two major structural proteins, which correspond to gpFI (tail sheath) and gpFII (tail tube) of P2 phage, respectively. We found that maltocin P28 had bactericidal activity against 38 of 81 testedS. maltophiliastrains. Therefore, maltocin P28 is a promising therapeutic substitute for antibiotics forS. maltophiliainfections.


2019 ◽  
Author(s):  
Sheyda Azimi ◽  
Aled E. L. Roberts ◽  
Shengyun Peng ◽  
Joshua S. Weitz ◽  
Alan McNally ◽  
...  

AbstractPseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported, however, the impact of heterogeneity on social behaviors and community function is poorly understood. Here we describe how this heterogeneity impacts on behavioral traits by evolving the strain PAO1 in biofilms grown in a synthetic sputum medium for 50 days. We measured social trait production and antibiotic tolerance and used a metagenomic approach to analyze and assess genomic changes over the duration of the evolution experiment. We found that (i) evolutionary trajectories were reproducible in independently evolving populations; (ii) over 60% of genomic diversity occurred within the first 10 days of selection. We then focused on quorum sensing (QS), a well-studied P. aeruginosa trait that is commonly mutated in strains isolated from CF lungs. We found that at the population level (i) evolution in sputum medium selected for decreased production of QS and QS-dependent traits; (ii) there was a significant correlation between lasR mutant frequency, the loss of protease and the 3O-C12-HSL signal, and an increase in resistance to clinically relevant β-lactam antibiotics, despite no previous antibiotic exposure. Overall, our findings provide insights into the effect of allelic polymorphism on community functions in diverse P. aeruginosa populations. Further, we demonstrate that P. aeruginosa population and evolutionary dynamics can impact on traits important for virulence and can lead to increased tolerance to β-lactam antibiotics.


Author(s):  
Shannon R. Coleman ◽  
Manjeet Bains ◽  
Maren L. Smith ◽  
Victor Spicer ◽  
Ying Lao ◽  
...  

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that undergoes swarming motility in response to semisolid conditions with amino acids as a nitrogen source. With a genome encoding hundreds of potential intergenic small RNAs (sRNAs), P. aeruginosa can easily adapt to different conditions and stresses. We previously identified 20 sRNAs that were differentially expressed under swarming conditions. Here, these sRNA were overexpressed in strain PAO1 and subjected to an array of phenotypic screens. Overexpression of PrrH resulted in decreased swimming motility; while a ΔprrH mutant had decreased cytotoxicity and increased pyoverdine production. Overexpression of the previously uncharacterized PA2952.1 resulted in decreased swarming and swimming motilities, increased gentamicin and tobramycin resistance under swarming conditions, and increased trimethoprim susceptibility. RNA-Seq and proteomics were performed on the wildtype overexpressing PA2952.1 cf. the empty vector control under swarming conditions, and revealed the differential expression (FC ≥ ±1.5) of 784 genes and the differential abundance (FC ≥ ±1.25) of 59 proteins. Amongst these were found 73 transcriptional regulators, two-component systems and sigma and anti-sigma factors. Downstream effectors included downregulated pili and flagellar genes, the upregulated efflux pump MexGHI-OpmD, and the upregulated arn operon. Genes involved in iron and zinc uptake were generally upregulated, and certain pyoverdine genes were upregulated. Overall, the sRNAs PA2952.1 and PrrH appeared to be involved in regulating virulence-related programs in P. aeruginosa, including iron acquisition and motility. IMPORTANCE Due to the rising incidence of multidrug-resistant strains and the difficulty of eliminating P. aeruginosa infections, it is important to understand the regulatory mechanisms that allow this bacterium to adapt to and thrive under a variety of conditions. Small RNAs (sRNAs) are one regulatory mechanism that allow bacteria to change the amount of protein synthesized. In this study, we overexpressed 20 different sRNAs in order to investigate how this might affect different bacterial behaviours. We found that one of the sRNAs, PrrH, played a role in swimming motility and virulence phenotypes, indicating a potentially important role in clinical infections. Another sRNA, PA2952.1, affected other clinically relevant phenotypes, including motility and antibiotic resistance. RNA-Seq and proteomics of the strain overexpressing PA2952.1 revealed the differential expression of 784 genes and 59 proteins, with a total of 73 regulatory factors. This substantial dysregulation indicates an important role for the sRNA PA2952.1.


2021 ◽  
Vol 10 (43) ◽  
Author(s):  
Miseon Park ◽  
Christine V. Summage-West ◽  
Lillie M. Sims ◽  
Sung-Guk Kim

Stenotrophomonas maltophilia is an emerging opportunistic pathogen that is frequently associated with hospital infections. We report the 4.8-Mbp draft genome sequence of the oxidase-positive S. maltophilia strain N0320, an isolate from a commercial hydroxyapatite nanoparticle product.


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