scholarly journals The global phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia

2019 ◽  
Author(s):  
Matthias I Gröschel ◽  
Conor J Meehan ◽  
Ivan Barilar ◽  
Margo Diricks ◽  
Aitor Gonzaga ◽  
...  
Keyword(s):  
Population Structure ◽  
Resistance Genes ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Global Level ◽  
Global Spread ◽  
Healthcare Associated ◽  
Globally Distributed ◽  
Hospital Transmission

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.

Substances based on natural fungal compounds inhibit the biofilm of various Stenotrophomonas maltophilia isolates

2020 ◽  
Author(s):  
Mirja Gudzuhn ◽  
Ifey Alio ◽  
Jörg Steinmann ◽  
Nina Schützenmeister ◽  
Wolfgang R. Streit
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Opportunistic Pathogen ◽  
Microtiter Plate ◽  
Multidrug Resistant ◽  
Reduction Effect ◽  
Biofilm Structure ◽  
The Impact ◽  
Globally Distributed ◽  
Human Specific

<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>

scholarly journals Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Maria F. Mojica ◽  
Krisztina M. Papp-Wallace ◽  
Magdalena A. Taracila ◽  
Melissa D. Barnes ◽  
Joseph D. Rutter ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
World Health ◽  
Combination Therapies ◽  
Content Type ◽  
Medical Need ◽  
The World ◽  
Health Organization

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.

scholarly journals Successful Treatment of Bloodstream Infection Due to Metallo-β-Lactamase-Producing Stenotrophomonas maltophilia in a Renal Transplant Patient

2016 ◽  
Vol 60 (9) ◽  
pp. 5130-5134 ◽  
Author(s):  
Maria F. Mojica ◽  
Christopher P. Ouellette ◽  
Amy Leber ◽  
M. Brian Becknell ◽  
Monica I. Ardura ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Stenotrophomonas Maltophilia ◽  
Conventional Treatment ◽  
Renal Transplant Patient ◽  
Transplant Patient ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Content Type ◽  
Colistimethate Sodium ◽  
Novel Drug

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.

scholarly journals WGS based study of the population structure of Salmonella enterica serovar Infantis

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Pernille Gymoese ◽  
Kristoffer Kiil ◽  
Mia Torpdahl ◽  
Mark T. Østerlund ◽  
Gitte Sørensen ◽  
...  
Keyword(s):  
Population Structure ◽  
Resistance Genes ◽  
Multidrug Resistant ◽  
Food Sources ◽  
Animal Origin ◽  
Multiple Resistance ◽  
Snp Analysis ◽  
Infectious Clones ◽  
Genetic Clusters ◽  
Multiple Resistance Genes

Abstract Background Salmonella Infantis (S. Infantis) is one of the most frequent Salmonella serovars isolated from human cases of salmonellosis and the most detected serovar from animal and food sources in Europe. The serovar is commonly associated with poultry and there is increasing concern over multidrug resistant clones spreading worldwide, as the dominating clones are characterized by presence of large plasmids carrying multiple resistance genes. Increasing the knowledge of the S. Infantis population and evolution is important for understanding and preventing further spread. In this study, we analysed a collection of strains representing different decades, sources and geographic locations. We analysed the population structure and the accessory genome, in particular we identified prophages with a view to understand the role of prophages in relation to the evolution of this serovar. Results We sequenced a global collection of 100 S. Infantis strains. A core-genome SNP analysis separated five strains in e-Burst Group (eBG) 297 with a long branch. The remaining strains, all in eBG31, were divided into three lineages that were estimated to have separated approximately 150 years ago. One lineage contained the vast majority of strains. In five of six clusters, no obvious correlation with source or geographical locations was seen. However, one cluster contained mostly strains from human and avian sources, indicating a clone with preference for these sources. The majority of strains within this cluster harboured a pESI-like plasmid with multiple resistance genes. Another lineage contained three genetic clusters with more rarely isolated strains of mainly animal origin, possibly less sampled or less infectious clones. Conserved prophages were identified in all strains, likely representing bacteriophages which integrated into the chromosome of a common ancestor to S. Infantis. We also saw that some prophages were specific to clusters and were probably introduced when the clusters were formed. Conclusions This study analysed a global S. Infantis population and described its genetic structure. We hypothesize that the population has evolved in three separate lineages, with one more successfully emerging lineage. We furthermore detected conserved prophages present in the entire population and cluster specific prophages, which probably shaped the population structure.

scholarly journals Characterization of Maltocin P28, a Novel Phage Tail-Like Bacteriocin from Stenotrophomonas maltophilia

2013 ◽  
Vol 79 (18) ◽  
pp. 5593-5600 ◽  
Author(s):  
Jian Liu ◽  
Peng Chen ◽  
Congyi Zheng ◽  
Yu-Ping Huang
Keyword(s):  
Gene Cluster ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Gene Organization ◽  
Open Reading Frames ◽  
Proteinase K ◽  
Major Protein ◽  
Content Type ◽  
Phage Tail

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.

scholarly journals Innate Host Defense against Klebsiella pneumoniae and the Outlook for Development of Immunotherapies

2021 ◽  
pp. 1-15
Author(s):  
Clement Opoku-Temeng ◽  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Frank R. DeLeo
Keyword(s):  
Klebsiella Pneumoniae ◽  
Host Defense ◽  
Severe Disease ◽  
Treatment Options ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Severe Illness ◽  
Preventative Measures ◽  
Number Of Treatment ◽  
Healthcare Associated

<i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) is a Gram-negative commensal bacterium and opportunistic pathogen. In healthy individuals, the innate immune system is adept at protecting against <i>K. pneumoniae</i> infection. Notably, the serum complement system and phagocytic leukocytes (e.g., neutrophils) are highly effective at eliminating <i>K. pneumoniae</i> and thereby preventing severe disease. On the other hand, the microbe is a major cause of healthcare-associated infections, especially in individuals with underlying susceptibility factors, such as pre-existing severe illness or immune suppression. The burden of <i>K. pneumoniae</i> infections in hospitals is compounded by antibiotic resistance. Treatment of these infections is often difficult largely because the microbes are usually resistant to multiple antibiotics (multidrug resistant [MDR]). There are a limited number of treatment options for these infections and new therapies, and preventative measures are needed. Here, we review host defense against <i>K. pneumoniae</i> and discuss recent therapeutic measures and vaccine approaches directed to treat and prevent severe disease caused by MDR <i>K. pneumoniae</i>.

scholarly journals The Epidome - A species-specific Approach to Assess the Population Structure and Heterogeneity of Staphylococcus Epidermidis Colonization and Infection

2020 ◽  
Author(s):  
Amalie Katrine Rendboe ◽  
Thor Bech Johannesen ◽  
Anna Cäcilia Ingham ◽  
Emeli Månsson ◽  
Søren Iversen ◽  
...  
Keyword(s):  
Population Structure ◽  
Staphylococcus Epidermidis ◽  
Temporal Stability ◽  
Amplicon Sequencing ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Species Level ◽  
Absolute Abundance ◽  
Variable Regions ◽  
High Degree

Abstract BackgroundAlthough generally known as a human commensal, Staphylococcus epidermidis is also an opportunistic pathogen that can cause nosocomial infections related to foreign body materials and immunicompromized patients. Infections are often caused by multidrug resistant (MDR) lineages that are difficult and costly to treat, and can have a major adverse impact on patients’ quality of life. Heterogeneity is a common phenomenon in both carriage and infection, but present methodology for detection of this is laborious or expensive. In this study, we present a culture-independent method, labelled Epidome, based on an amplicon sequencing-approach to deliver information beyond species level on primary samples and to elucidate clonality, population structure and temporal stability or niche selection of S. epidermidis communities. MethodsBased on an assessment of >800 genes from the S. epidermidis core genome, we identified genes with variable regions, which in combination facilitated the differentiation of phylogenetic clusters observed in silico, and allowed classification down to lineage level. A duplex PCR, combined with an amplicon sequencing protocol, and a downstream analysis pipeline were designed to provide subspecies information from primary samples. Additionally, a probe-based qPCR was designed to provide valuable absolute abundance quantification of S. epidermidis. ResultsA combined laboratory and bioinformatic approach was successfully designed and validated on isolates representing skin commensals and on genomic mock communities to validate primer specificity and reproducibility using technical replicates. The method was furthermore applied to a sample set of primary skin and nasal samples, revealing a high degree of heterogeneity in the S. epidermidis population at both sampling sites with resolution down to distinct lineages. Additionally, the qPCR, with a detection limit of <10 copies/µL, showed a high degree of variation in absolute abundance of S. epidermidis.ConclusionsThe Epidome method is designed for use on primary samples to obtain information on S. epidermidis abundance and diversity beyond species-level to answer important questions regarding the emergence and dissemination of nosocomial lineages, investigating clonality of S. epidermidis communities, population dynamics, and niche selection. Our targeted-sequencing method allows rapid differentiation and identification of clinically important nosocomial lineages in primary low-biomass samples such as skin samples.

Prevalence of trimethoprim/sulfamethoxazole resistance genes among Stenotrophomonas maltophilia clinical isolates in Egypt

2021 ◽  
Author(s):  
Amel Elsheredy ◽  
Azza Elsheikh ◽  
Abeer Ghazal ◽  
Sherine Shawky
Keyword(s):  
Resistance Genes ◽  
Surveillance System ◽  
Stenotrophomonas Maltophilia ◽  
Insertion Sequence ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Nosocomial Pathogen ◽  
Drug Of Choice

Abstract Stenotrophomonas maltophilia is an important multidrug resistant nosocomial pathogen. Trimethoprim/sulfamethoxazole (TMP/SMX) is considered the drug of choice for treatment of S. maltophilia infections, thus emerging resistance to TMP/SMX poses a serious threat. In the present study we aimed to investigate the frequency of TMP/SMX resistance genes (sul1, sul2, dfrA), and to evaluate their relatedness with integron 1 (int1), and insertion sequence common regions (ISCR) among 100 S. maltophilia from different clinical isolates in Egypt. Isolates were identified biochemically and confirmed by VITEK2. Detection of sul1, sul2, and dfrA genes, int1 and ISCR elements was performed by PCR. Among the 16 TMP/SMX resistant isolates, sul1 gene was detected in all of them, and it was associated with int1 gene presence in all resistant isolates. The sul2 gene was detected in 6 out of 16 resistant isolates (37.5%), and only 2 of the 16 resistant isolates (12.5%) harboured dfrA gene. ISCR was detected in 10 of the resistant isolates (62.5%) and in 4 of them it was associated with the presence of sul2 gene. Among the 84 TMP/SMX sensitive isolates, sul1 gene was detected in 15 (17.8%), int1 in 16 (19%) and ISCR in 6 (7.1%). None of the susceptible isolates had sul2 or dfrA genes. These findings point out an increasing frequency of TMP/SMX resistance genes among S. maltophilia clinical isolates in our region, so the adoption of prudent use of S. maltophilia antimicrobial agents and the establishment of a surveillance system are desperately needed.

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