Global analyses imply that Stenotrophomonas maltophilia biofilms are phenotypically highly diverse despite a common transcriptome profile

2020 ◽  
Author(s):  
Ifey Alio ◽  
Mirja Gudzuhn ◽  
Marie Schölmerich ◽  
Pablo Pérez García ◽  
Christel Vollstedt ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Stenotrophomonas Maltophilia ◽  
Phenotypic Variability ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
Data Set ◽  
Specific Level ◽  
Key Factor ◽  
Fermentative Growth

<p><strong>Stenotrophomonas maltophilia</strong><strong> is one of the most frequently isolated multidrug resistant opportunistic pathogens. It contributes to disease progression in cystic fibrosis patients and is found in wounds, other infected tissues and on catheter surfaces. Only little is known on key processes linked to biofilm formation of S. maltophilia on a broader basis. Thus the aim of this study was the identification of key processes involved in biofilm formation of S. maltophilia on a global level. Therefore, we analyzed biofilm profiles of 300 globally collected clinical and environmental isolates of the main and recently identified lineages Sgn3, Sgn4 and Sm2 - Sm18 (Groeschel et al., 2020). These data together with the 3D structural analysis of a subset of clinical 40 clinical isolates revealed an unexpectedly high phenotypic variability on a strain specific level. Further transcriptome analysis of seven clinical isolates using biofilm grown cells identified a set of 106 shared and coexpressed genes and roughly 30-35 strain-specific genes. Based on these findings S. maltophilia employs a mostly fermentative growth modus under the biofilm conditions and uptake of iron, phosphorous and other metals appears to be of high relevance. Surprisingly, the transcriptome profiles of biofilm versus planktonic cells revealed that only 8.6% of all genes were differentially regulated when both conditions were compared.  This implies that only relatively few genes contribute to the change from planktonic to biofilm life style. Thereby iron uptake appears to be a key factor involved in this metabolic shift. The transcriptome data generated in this study together with the phenotypic and metabolic analysis represent so far the largest data set on S. maltophilia biofilm versus planktonic grown cells. This study now lays the foundation for the identification of new strategies in fighting S. maltophilia infections in clinical settings.</strong></p> <p>Ref:  Gröschel et al., 2020 ,The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia. Nature Commun. 2020 Apr 27;11(1):2044. doi: 10.1038/s41467-020-15123-0.</p>

scholarly journals Phenotypic and Transcriptomic Analyses of Seven Clinical Stenotrophomonas maltophilia Isolates Identify a Small Set of Shared and Commonly Regulated Genes Involved in the Biofilm Lifestyle

2020 ◽  
Vol 86 (24) ◽  
Author(s):  
Ifey Alio ◽  
Mirja Gudzuhn ◽  
Pablo Pérez García ◽  
Dominik Danso ◽  
Marie Charlotte Schoelmerich ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Antimicrobial Agents ◽  
Phenotypic Variability ◽  
Single Species ◽  
Clinical Isolates ◽  
Planktonic Cells ◽  
Data Set ◽  
Specific Level ◽  
Content Type ◽  
Small Set

ABSTRACT Stenotrophomonas maltophilia is one of the most frequently isolated multidrug-resistant nosocomial opportunistic pathogens. It contributes to disease progression in cystic fibrosis (CF) patients and is frequently isolated from wounds, infected tissues, and catheter surfaces. On these diverse surfaces S. maltophilia lives in single-species or multispecies biofilms. Since very little is known about common processes in biofilms of different S. maltophilia isolates, we analyzed the biofilm profiles of 300 clinical and environmental isolates from Europe of the recently identified main lineages Sgn3, Sgn4, and Sm2 to Sm18. The analysis of the biofilm architecture of 40 clinical isolates revealed the presence of multicellular structures and high phenotypic variability at a strain-specific level. Further, transcriptome analyses of biofilm cells of seven clinical isolates identified a set of 106 shared strongly expressed genes and 33 strain-specifically expressed genes. Surprisingly, the transcriptome profiles of biofilm versus planktonic cells revealed that just 9.43% ± 1.36% of all genes were differentially regulated. This implies that just a small set of shared and commonly regulated genes is involved in the biofilm lifestyle. Strikingly, iron uptake appears to be a key factor involved in this metabolic shift. Further, metabolic analyses implied that S. maltophilia employs a mostly fermentative growth mode under biofilm conditions. The transcriptome data of this study together with the phenotypic and metabolic analyses represent so far the largest data set on S. maltophilia biofilm versus planktonic cells. This study will lay the foundation for the identification of strategies for fighting S. maltophilia biofilms in clinical and industrial settings. IMPORTANCE Microorganisms living in a biofilm are much more tolerant to antibiotics and antimicrobial substances than planktonic cells are. Thus, the treatment of infections caused by microorganisms living in biofilms is extremely difficult. Nosocomial infections (among others) caused by S. maltophilia, particularly lung infection among CF patients, have increased in prevalence in recent years. The intrinsic multidrug resistance of S. maltophilia and the increased tolerance to antimicrobial agents of its biofilm cells make the treatment of S. maltophilia infection difficult. The significance of our research is based on understanding the common mechanisms involved in biofilm formation of different S. maltophilia isolates, understanding the diversity of biofilm architectures among strains of this species, and identifying the differently regulated processes in biofilm versus planktonic cells. These results will lay the foundation for the treatment of S. maltophilia biofilms.

scholarly journals The Toxin-Antitoxin Systems of the Opportunistic Pathogen Stenotrophomonas maltophilia of Environmental and Clinical Origin

Toxins ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 635
Author(s):  
Laurita Klimkaitė ◽  
Julija Armalytė ◽  
Jūratė Skerniškytė ◽  
Edita Sužiedėlienė
Keyword(s):  
Biofilm Formation ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Bioinformatic Analysis ◽  
Multidrug Resistant ◽  
Bacterial Toxin ◽  
Clinical Settings ◽  
Environmental Bacterium ◽  
Tract Infections

Stenotrophomonas maltophilia is a ubiquitous environmental bacterium that has recently emerged as a multidrug-resistant opportunistic pathogen causing bloodstream, respiratory, and urinary tract infections. The connection between the commensal environmental S. maltophilia and the opportunistic pathogen strains is still under investigation. Bacterial toxin–antitoxin (TA) systems have been previously associated with pathogenic traits, such as biofilm formation and resistance to antibiotics, which are important in clinical settings. The same species of the bacterium can possess various sets of TAs, possibly influencing their overall stress response. While the TA systems of other important opportunistic pathogens have been researched, nothing is known about the TA systems of S. maltophilia. Here, we report the identification and characterization of S. maltophilia type II TA systems and their prevalence in the isolates of clinical and environmental origins. We found 49 putative TA systems by bioinformatic analysis in S. maltophilia genomes. Despite their even spread in sequenced S. maltophilia genomes, we observed that relBE, hicAB, and previously undescribed COG3832-ArsR operons were present solely in clinical S. maltophilia isolates collected in Lithuania, while hipBA was more frequent in the environmental ones. The kill-rescue experiments in Escherichia coli proved higBA, hicAB, and relBE systems to be functional TA modules. Together with different TA profiles, the clinical S. maltophilia isolates exhibited stronger biofilm formation, increased antibiotic, and serum resistance compared to environmental isolates. Such tendencies suggest that certain TA systems could be used as indicators of virulence traits.

scholarly journals Enhancement of pyocyanin production by subinhibitory concentration of royal jelly in Pseudomonas aeruginosa

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 14
Author(s):  
Dina Auliya Amly ◽  
Puspita Hajardhini ◽  
Alma Linggar Jonarta ◽  
Heribertus Dedy Kusuma Yulianto ◽  
Heni Susilowati
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Growth ◽  
Biofilm Formation ◽  
Royal Jelly ◽  
Microtiter Plate ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Antibiotic Tolerance ◽  
Subinhibitory Concentration ◽  
Pyocyanin Production

Background: Pseudomonas aeruginosa, a multidrug-resistant Gram-negative bacterium, produces pyocyanin, a virulence factor associated with antibiotic tolerance. High concentrations of royal jelly have an antibacterial effect, which may potentially overcome antibacterial resistance. However, in some cases, antibiotic tolerance can occur due to prolonged stress of low-dose antibacterial agents. This study aimed to investigate the effect of subinhibitory concentrations of royal jelly on bacterial growth, pyocyanin production, and biofilm formation of P. aeruginosa. Methods: Pseudomonas aeruginosa ATCC 10145 and clinical isolates were cultured in a royal jelly-containing medium to test the antibacterial activity. Pyocyanin production was observed by measuring the absorbance at 690 nm after 36 h culture and determined using extinction coefficient 4310 M-1 cm-1. Static microtiter plate biofilm assay performed to detect the biofilm formation, followed by scanning electron microscopy. Results: Royal jelly effectively inhibited the viability of both strains from a concentration of 25%. The highest production of pyocyanin was observed in the subinhibitory concentration group 6.25%, which gradually decreased along with the decrease of royal jelly concentration. Results of one-way ANOVA tests differed significantly in pyocyanin production of the two strains between the royal jelly groups. Tukey HSD test showed concentrations of 12.5%, 6.25%, and 3.125% significantly increased pyocyanin production of ATCC 10145, and the concentrations of 12.5% and 6.25% significantly increased production of the clinical isolates. Concentrations of 12.5% and 6.125% significantly induced biofilm formation of P. aeruginosa ATCC 10145, in line with the results of the SEM analysis. Conclusions: The royal jelly concentration of 25% or higher inhibits bacterial growth; however, the subinhibitory concentration increases pyocyanin production and biofilm formation in P. aeruginosa. It is advisable to determine the appropriate concentration of royal jelly to obtain beneficial virulence inhibiting activity.

Higher biofilm formation in multidrug-resistant clinical isolates of Staphylococcus aureus

2008 ◽  
Vol 32 (1) ◽  
pp. 68-72 ◽  
Author(s):  
An Sung Kwon ◽  
Gwang Chul Park ◽  
So Yeon Ryu ◽  
Dong Hoon Lim ◽  
Dong Yoon Lim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Clinical Isolates

scholarly journals Stenotrophomonas maltophilia strains replicate and persist in the murine lung, but to significantly different degrees

Microbiology ◽  
2011 ◽  
Vol 157 (7) ◽  
pp. 2133-2142 ◽  
Author(s):  
Ruella Rouf ◽  
Sara M. Karaba ◽  
Jenny Dao ◽  
Nicholas P. Cianciotto
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Mouse Strains ◽  
Mammalian Host ◽  
Virulence Determinants ◽  
Environmental Bacterium ◽  
Bacterial Replication ◽  
Pro Inflammatory Cytokines

The environmental bacterium Stenotrophomonas maltophilia is increasingly described as a multidrug-resistant pathogen of humans, being associated with pneumonia, among other diseases. But the degree to which S. maltophilia is capable of replicating in a mammalian host has been an issue of controversy. Using a model of intranasal inoculation into adult A/J mice, we now document that S. maltophilia strain K279a, the clinical isolate of S. maltophilia whose complete genome sequence was recently determined, is in fact capable of replicating in lungs, displaying as much as a 10-fold increase in c.f.u. in the first 8 h of infection. Importantly, as few as 104 c.f.u. deposited into the A/J lung was sufficient to promote bacterial outgrowth. Bacterial replication in the lungs of the A/J mice was followed by elevations in pro-inflammatory cytokines and also promoted resistance to subsequent challenge. We also found that DBA/2 mice were permissive for S. maltophilia K279a replication, although the level of growth and persistence in these animals was less than it was in the A/J mice. In contrast, the BALB/c and C57BL/6 mouse strains were non-permissive for S. maltophilia K279a growth. Interestingly, when five additional clinical isolates were introduced into the A/J lung, marked differences in survival were observed, with some strains being much less infective than K279a and others being appreciably more infective. These data suggest that the presence of major virulence determinants is variable among clinical isolates. Overall, this study confirms the infectivity of S. maltophilia for the mammalian host, and illustrates how both host and bacterial factors affect the outcome of Stenotrophomonas infection.

scholarly journals Decreased expression of femXAB genes and fnbp mediated biofilm pathways in OS-MRSA clinical isolates

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Umarani Brahma ◽  
Paresh Sharma ◽  
Shweta Murthy ◽  
Savitri Sharma ◽  
Shalini Chakraborty ◽  
...  
Keyword(s):  
Antibiotic Susceptibility ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Agglutination Test ◽  
Clinical Isolates ◽  
Ocular Infections ◽  
Biofilm Production ◽  
Fibronectin Binding ◽  
Sequence Types

Abstract Methicillin-Resistant Staphylococcus aureus (MRSA) is a significant threat to human health. Additionally, biofilm forming bacteria becomes more tolerant to antibiotics and act as bacterial reservoir leading to chronic infection. In this study, we characterised the antibiotic susceptibility, biofilm production and sequence types (ST) of 74 randomly selected clinical isolates of S. aureus causing ocular infections. Antibiotic susceptibility revealed 74% of the isolates as resistant against one or two antibiotics, followed by 16% multidrug-resistant isolates (MDR), and 10% sensitive. The isolates were characterized as MRSA (n = 15), Methicillin-sensitive S. aureus (MSSA, n = 48) and oxacillin susceptible mecA positive S. aureus (OS-MRSA, n = 11) based on oxacillin susceptibility, mecA gene PCR and PBP2a agglutination test. All OS-MRSA would have been misclassified as MSSA on the basis of susceptibility test. Therefore, both phenotypic and genotypic tests should be included to prevent strain misrepresentation. In addition, in-depth studies for understanding the emerging OS-MRSA phenotype is required. The role of fem XAB gene family has been earlier reported in OS-MRSA phenotype. Sequence analysis of the fem XAB genes revealed mutations in fem × (K3R, H11N, N18H and I51V) and fem B (L410F) genes. The fem XAB genes were also found down-regulated in OS-MRSA isolates in comparison to MRSA. In OS-MRSA isolates, biofilm formation is regulated by fibronectin binding proteins A & B. Molecular typing of the isolates revealed genetic diversity. All the isolates produced biofilm, however, MRSA isolates with strong biofilm phenotype represent a worrisome situation and may even result in treatment failure.

scholarly journals Drug Resistance and Biofilm Production among Pseudomonas aeruginosa Clinical Isolates in a Tertiary Care Hospital of Nepal

2019 ◽  
Vol 21 (2) ◽  
pp. 110-116
Author(s):  
Rajani Shrestha ◽  
N. Nayak ◽  
D.R. Bhatta ◽  
D. Hamal ◽  
S.H. Subramanya ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Biofilm Formation ◽  
Tertiary Care ◽  
Clinical Problem ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Diffusion Method ◽  
Care Hospital ◽  
Microbiological Methods

Clinical isolates of Pseudomonas aeruginosa often exhibit multidrug resistance due to their inherent ability to form biofilms. Drug resistance in Ps. aeruginosa is a major clinical problem, especially in the management of patients with nosocomial infections and those admitted to ICUs with indwelling medical devices. To evaluate the biofilm forming abilities of the clinical isolates of Ps. aeruginosa and to correlate biofilm formation with antibiotic resistance. A total of 90 consecutive isolates of Ps. aeruginosa obtained from various specimens collected from patients visiting the Manipal Teaching Hospital, Pokhara, Nepal between January 2018 - October 2018 were studied. Isolates were identified by standard microbiological methods. Antibiotic susceptibility testing was performed by Kirby-Bauer disc diffusion method. All the isolates were tested for their biofilm forming abilities by employing the tissue culture plate assay. Of the 90 Ps. aeruginosa isolates, maximum i.e 42 (46.6%) were from patients in the age group of > 50 years. Majority (30; 33.3%) of the isolates were obtained from sputum samples. However, percentage isolation from other specimens like urine, endotracheal tube (ETT), pus, eye specimens and blood were 18.9%, 16.7%, 16.7%, 7.8% and 6.7% respectively. All the isolates were sensitive to polymixin B and colistin, 91.1% of the organisms were sensitive to imipenem, and more than 80% to aminoglycosides (80% to gentamicin, 83.3% to amikacin). A total of 29 (32.2%) organisms were biofilm producers. Maximum numbers of biofilm producing strains were obtained from ETT (8 of 15; 53.3%), pus (8 of 15; 53.3%) and blood (2 of 6; 33.3%) i.e from all invasive sites. None of the isolates from noninvasive specimens such as conjunctival swabs were biofilm positive. Significantly higher numbers of biofilm producers (23 of 29; 79.3%) were found to be multidrug resistant as compared to non-biofilm (6 of 61; 9.8%) producers (p=0.000). Ps. aeruginosa colonization leading to biofilm formation in deep seated tissues and on indwelling devices is a therapeutic challenge as majority of the isolates would be recalcitrant to commonly used antipseudomonal drugs. Effective monitoring of drug resistance patterns in all Pseudomonas clinical isolates should be a prerequisite for successful patient management.

scholarly journals Enhancement of pyocyanin production by subinhibitory concentration of royal jelly in Pseudomonas aeruginosa

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 14
Author(s):  
Dina Auliya Amly ◽  
Puspita Hajardhini ◽  
Alma Linggar Jonarta ◽  
Heribertus Dedy Kusuma Yulianto ◽  
Heni Susilowati
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Growth ◽  
Biofilm Formation ◽  
Royal Jelly ◽  
Microtiter Plate ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Antibiotic Tolerance ◽  
Subinhibitory Concentration ◽  
Pyocyanin Production

Background: Pseudomonas aeruginosa, a multidrug-resistant Gram-negative bacterium, produces pyocyanin, a virulence factor associated with antibiotic tolerance. High concentrations of royal jelly have an antibacterial effect, which may potentially overcome antibacterial resistance. However, in some cases, antibiotic tolerance can occur due to prolonged stress of low-dose antibacterial agents. This study aimed to investigate the effect of subinhibitory concentrations of royal jelly on bacterial growth, pyocyanin production, and biofilm formation of P. aeruginosa. Methods: Pseudomonas aeruginosa ATCC 10145 and clinical isolates were cultured in a royal jelly-containing medium to test the antibacterial activity. Pyocyanin production was observed by measuring the absorbance at 690 nm after 36 h culture and determined using extinction coefficient 4310 M-1 cm-1. Static microtiter plate biofilm assay performed to detect the biofilm formation, followed by scanning electron microscopy. Results: Royal jelly effectively inhibited the viability of both strains from a concentration of 25%. The highest production of pyocyanin was observed in the subinhibitory concentration group 6.25%, which gradually decreased along with the decrease of royal jelly concentration. Results of one-way ANOVA tests differed significantly in pyocyanin production of the two strains between the royal jelly groups. Tukey HSD test showed concentrations of 12.5%, 6.25%, and 3.125% significantly increased pyocyanin production of ATCC 10145, and the concentrations of 12.5% and 6.25% significantly increased production of the clinical isolates. Concentrations of 12.5% and 6.125% significantly induced biofilm formation of P. aeruginosa ATCC 10145, in line with the results of the SEM analysis. Conclusions: The royal jelly concentration of 25% or higher inhibits bacterial growth; however, the subinhibitory concentration increases pyocyanin production and biofilm formation in P. aeruginosa. It is advisable to determine the appropriate concentration of royal jelly to obtain beneficial virulence inhibiting activity.

scholarly journals Thiostrepton Hijacks Pyoverdine Receptors To Inhibit Growth ofPseudomonas aeruginosa

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Michael R. M. Ranieri ◽  
Derek C. K. Chan ◽  
Luke N. Yaeger ◽  
Madeleine Rudolph ◽  
Sawyer Karabelas-Pittman ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Dependent Manner ◽  
Peptide Antibiotics ◽  
Iron Starvation ◽  
Gram Negative ◽  
Content Type

ABSTRACTPseudomonas aeruginosais a biofilm-forming opportunistic pathogen and is intrinsically resistant to many antibiotics. In a high-throughput screen for molecules that modulate biofilm formation, we discovered that the thiopeptide antibiotic thiostrepton (TS), which is considered to be inactive against Gram-negative bacteria, stimulatedP. aeruginosabiofilm formation in a dose-dependent manner. This phenotype is characteristic of exposure to antimicrobial compounds at subinhibitory concentrations, suggesting that TS was active againstP. aeruginosa. Supporting this observation, TS inhibited the growth of a panel of 96 multidrug-resistant (MDR)P. aeruginosaclinical isolates at low-micromolar concentrations. TS also had activity againstAcinetobacter baumanniiclinical isolates. The expression of Tsr, a 23S rRNA-modifying methyltransferase from TS producerStreptomyces azureus, intransconferred TS resistance, confirming that the drug acted via its canonical mode of action, inhibition of ribosome function. The deletion of oligopeptide permease systems used by other peptide antibiotics for uptake failed to confer TS resistance. TS susceptibility was inversely proportional to iron availability, suggesting that TS exploits uptake pathways whose expression is increased under iron starvation. Consistent with this finding, TS activity againstP. aeruginosaandA. baumanniiwas potentiated by the FDA-approved iron chelators deferiprone and deferasirox and by heat-inactivated serum. Screening ofP. aeruginosamutants for TS resistance revealed that it exploits pyoverdine receptors FpvA and FpvB to cross the outer membrane. We show that the biofilm stimulation phenotype can reveal cryptic subinhibitory antibiotic activity, and that TS has activity against select multidrug-resistant Gram-negative pathogens under iron-limited growth conditions, similar to those encountered at sites of infection.

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