scholarly journals Estimation of pathogenic potential of an environmental Pseudomonas aeruginosa isolate using comparative genomics

2020 ◽  
Author(s):  
Carola Berger ◽  
Christian Rückert ◽  
Jochen Blom ◽  
Korneel Rabaey ◽  
Jörn Kalinowski ◽  
...  

Abstract BackgroundNew strains of Pseudomonas aeruginosa are continuously being isolated and sequenced to increase the genomic accessibility of this important pathogen. This has led to the generation of an impressive dataset of closed P. aeruginosa genomes. To understand the difference between the strains, investigations are focused on the accessory genome, thereby constantly extending the known pan genome of P. aeruginosa as a species. Apart from follow-up studies, many of the publicly available genomes are only used in their original publication while additional in silico information, based on comparison to previously published genomes, is not being explored. In this study, we defined and investigated the genome of the environmental isolate P. aeruginosa KRP1 and compared it to more than 100 publicly available closed P. aeruginosa genomes. ResultsPseudomonas spp. KRP1 could clearly be identified as a P. aeruginosa isolate, via comparative genomics. By using different genomic island prediction programs, we could identify a total of 25 genomic islands that cover ~12% of the genome of P. aeruginosa KRP1. Based on intra-strain comparisons, we are able to predict the pathogenic potential of this environmental isolate. It shares a substantial amount of its genomic information with the highly virulent PSE9 and LESB58 strains. For both of these clones, their increased virulence has been directly linked to their accessory genome before. ConclusionsHere we show, how the integrated use of previously published genomic data today, can help to replace expensive and time consuming wetlab work to determine the pathogenetic potential of environmental isolates. This knowledge is vital to understand what makes an isolate a potential pathogen as it helps design effective treatment.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carola Berger ◽  
Christian Rückert ◽  
Jochen Blom ◽  
Korneel Rabaey ◽  
Jörn Kalinowski ◽  
...  

AbstractThe isolation and sequencing of new strains of Pseudomonas aeruginosa created an extensive dataset of closed genomes. Many of the publicly available genomes are only used in their original publication while additional in silico information, based on comparison to previously published genomes, is not being explored. In this study, we defined and investigated the genome of the environmental isolate P. aeruginosa KRP1 and compared it to more than 100 publicly available closed P. aeruginosa genomes. By using different genomic island prediction programs, we could identify a total of 17 genomic islands and 8 genomic islets, marking the majority of the accessory genome that covers ~ 12% of the total genome. Based on intra-strain comparisons, we are able to predict the pathogenic potential of this environmental isolate. It shares a substantial amount of genomic information with the highly virulent PSE9 and LESB58 strains. For both of these, the increased virulence has been directly linked to their accessory genome before. Hence, the integrated use of previously published data can help to minimize expensive and time consuming wetlab work to determine the pathogenetic potential.


2008 ◽  
Vol 190 (21) ◽  
pp. 7130-7140 ◽  
Author(s):  
Scott E. Battle ◽  
Folker Meyer ◽  
Jordi Rello ◽  
Vanderlene L. Kung ◽  
Alan R. Hauser

ABSTRACT Most known virulence determinants of Pseudomonas aeruginosa are remarkably conserved in this bacterium's core genome, yet individual strains differ significantly in virulence. One explanation for this discrepancy is that pathogenicity islands, regions of DNA found in some strains but not in others, contribute to the overall virulence of P. aeruginosa. Here we employed a strategy in which the virulence of a panel of P. aeruginosa isolates was tested in mouse and plant models of disease, and a highly virulent isolate, PSE9, was chosen for comparison by subtractive hybridization to a less virulent strain, PAO1. The resulting subtractive hybridization sequences were used as tags to identify genomic islands found in PSE9 but absent in PAO1. One 99-kb island, designated P. aeruginosa genomic island 5 (PAGI-5), was a hybrid of the known P. aeruginosa island PAPI-1 and novel sequences. Whereas the PAPI-1-like sequences were found in most tested isolates, the novel sequences were found only in the most virulent isolates. Deletional analysis confirmed that some of these novel sequences contributed to the highly virulent phenotype of PSE9. These results indicate that targeting highly virulent strains of P. aeruginosa may be a useful strategy for identifying pathogenicity islands and novel virulence determinants.


2020 ◽  
Author(s):  
Jose Arturo Molina-Mora ◽  
Diana Chinchilla-Montero ◽  
Raquel García Batán ◽  
Fernando García

Abstract Pseudomonas aeruginosa is an opportunist and versatile organism responsible for infections mainly in immunocompromised hosts. This pathogen has high intrinsic resistance to most antimicrobials. P. aeruginosa AG1 (PaeAG1) is a Costa Rican high-risk ST-111 strain with resistance to multiple antibiotics, including carbapenems, due to the activity of VIM-2 and IMP-18 metallo-β-lactamases (MBLs). These genes are harbored in two class 1 integrons located inone out of the 57 PaeAG1 genomic islands. However, the genomic context associated to these determinants in PaeAG1 and other P. aeruginosa strains is unclear. Thus, we first assessed the transcriptional activity of VIM-2 and IMP-18 genes when exposed to imipenem (a carbapenem) by RT-qPCR. To select related genomes to PaeAG1, we implemented a pan-genome analysis to define and up-date the phylogenetic relationship among complete P. aeruginosa genomes. We also studied the PaeAG1 genomic islands content in the related strains and finally we described the architecture and possible evolutionary steps of the genomic regions around the VIM-2- and IMP-18-carrying integrons.Expression of VIM-2 and IMP-18 genes was demonstrated to be induced after imipenem exposure. In a subsequent comparative genomics analysis with 211 strains, the P. aeruginosa pan-genome revealed that complete genome sequences are able to separate clones by MLST profile, including a clear ST-111 cluster with PaeAG1. The PaeAG1 genomic islands were found to define a diverse presence/absence pattern among related genomes. Finally, landscape reconstruction of genomic regions showed that VIM-2-carrying integron (In59-like) is an old-acquaintance element harbored in the same known region found in other two ST-111 strains. Also, PaeAG1 has an exclusive genomic region containing a novel IMP-18-carrying integron (registered as In1666), with an arrangement never reported before. Altogether, we provide new insights about the genomic determinants associated with the resistance to carbapenems in this high-risk P. aeruginosa using comparative genomics.


Crisis ◽  
2020 ◽  
Vol 41 (6) ◽  
pp. 422-428 ◽  
Author(s):  
Masatsugu Orui

Abstract. Background: Monitoring of suicide rates in the recovery phase following a devastating disaster has been limited. Aim: We report on a 7-year follow-up of the suicide rates in the area affected by the Great East Japan Earthquake, which occurred in March 2011. Method: This descriptive study covered the period from March 2009 to February 2018. Period analysis was used to divide the 108-month study period into nine segments, in which suicide rates were compared with national averages using Poisson distribution. Results: Male suicide rates in the affected area from March 2013 to February 2014 increased to a level higher than the national average. After subsequently dropping, the male rates from March 2016 to February 2018 re-increased and showed a greater difference compared with the national averages. The difference became significant in the period from March 2017 to February 2018 ( p = .047). Limitations: Specific reasons for increasing the rates in the recovery phase were not determined. Conclusion: The termination of the provision of free temporary housing might be influential in this context. Provision of temporary housing was terminated from 2016, which increased economic hardship among needy evacuees. Furthermore, disruption of the social connectedness in the temporary housing may have had an influence. Our findings suggest the necessity of suicide rate monitoring even in the recovery phase.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Syed A. K. Shifat Ahmed ◽  
Michelle Rudden ◽  
Sabrina M. Elias ◽  
Thomas J. Smyth ◽  
Roger Marchant ◽  
...  

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI’s) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 320.1-321
Author(s):  
E. Loibner ◽  
V. Ritschl ◽  
B. Leeb ◽  
P. Spellitz ◽  
G. Eichbauer-Sturm ◽  
...  

Background:Gender differences in prevalence and disease course are known in various rheumatic diseases; however, investigations of gender difference concerning therapeutical response have yielded variable results.Objectives:The aim of this retrospective study was to investigate, whether a gender difference in response rate to biological disease-modifying antirheumatic drugs (bDMARDs) and apremilast in bDMARD-naïve patients could be observed across the three most prevalent inflammatory arthritis diseases: rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA). Additionally, a response to individual TNF blockers was investigated in this respect.Methods:Data from bDMARD-naïve RA-, SpA- and PsA-patients from Bioreg, the Austrian registry for biological DMARDs in rheumatic diseases, were used. Patients with a baseline (Visit 1=V1) and follow-up visits at 6 months (Visit 2=V2) and 12 months (Visit 3=V3) were included and response to therapy with TNF-inhibitors (TNFi), furthermore to therapy with rituximab, tocilizumab and apremilast was analyzed according to gender. The remaining bDMARDs were not analyzed due to small numbers. Key response-parameter for RA was disease activity score (DAS28), whereas for PsoA the Stockerau Activity Score for Psoriatic Arthritis (SASPA) and for SpA the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were employed; in addition, the Health assessment Questionnaire (HAQ) was used. Data were analyzed in R Statistic stratified by gender using Kruskal-Wallis and Wilcoxon tests.Results:354 women and 123 men with RA (n=477), 81 women and 69 men with PsA (n=150), 121 women and 191 men with SpA (n=312) were included. No significant differences in biometrics was seen between female and male patients at baseline in all diseases.In RA patients overall DAS28 decreased from baseline (V1) to V2 and V3 (DAS28: V1: male: 4.38 [3.66, 5.11], female: 4.30 [3.68, 5.03], p(m/f) = 0.905; V2: male: 2.66 [1.73, 3.63], female: 3.10 [2.17, 3.98], p(m/f) = 0.015; V3: male: 2.25 [1.39, 3.36], female: 3.01 [1.87, 3.87], p(m/f) = 0.002). For TNF inhibitors (n=311), there was a significant difference between genders at V2 (Fig.1a). Patients receiving Rituximab (n=41) displayed a significantly higher DAS28 at baseline in females, which diminished in the follow up: V1: (p(m/f) p=0.002; V2: p=0.019; V3: p=0.13); response to tocilizumab (n=63) did not show any gender differences.In PsA patients overall SASPA decreased from baseline (V1) to V2 and V3 (SASPA: V1: male: 4.00 [2.80, 5.20], female: 4.40 [2.80, 5.80], p(m/f) = 0.399; V2: male: 2.20 [1.20, 3.50], female: 3.40 [2.00, 5.00], p(m/f) = 0.071; V3: male: 1.80 [0.80, 2.70], female: 3.01 [2.35, 4.80], p(m/f) = 0.001). For TNF inhibitors (n=79), there was a significant difference between genders at V3 (Fig 1a). For Apremilast (n=39), there was a significant difference between genders at V2 (Fig.1c).In SpA patients overall BASDAI decreased from baseline (V1) to V2 and V3 (BASDAI: V1: male: 4.70 [2.88, 6.18], female: 4.80 [3.30, 6.20], p(m/f) = 0.463; V2: male: 3.05 [2.00, 4.60], female: 3.64 [2.62, 5.41], p(m/f) = 0.039; V3: male: 3.02 [1.67, 4.20], female: 3.65 [2.18, 5.47], p(m/f) = 0.016). In V3 a differential BASDAI in response to TNFi (n=299) was observed (Fig.1a).Possible differences of response to individual TNFi (etanercept, infliximab, other TNFi) measured by HAQ were investigated in all diseases together. The difference between male and females was significant at baseline for all 3 TNFi; whereas with the use of ETA the significant difference was carried through to V2 and V3, it was lost with the use of IFX and was variable with the other TNFi (Fig.1b)Figure 1.Conclusion:Female patients showed a statistically lower response to TNFi in all three disease entities (RA, SpA and PsoA) to a variable degree in our homogenous central european population. Interestingly, the difference was not uniform across individual TNFi when measured by HAQ. Gender differences were also seen in response to Apremilast.Disclosure of Interests:Elisabeth Loibner: None declared, Valentin Ritschl: None declared, Burkhard Leeb Speakers bureau: AbbVie, Roche, MSD, Pfizer, Actiopharm, Boehringer-Ingelheim, Kwizda, Celgene, Sandoz, Grünenthal, Eli-Lilly, Grant/research support from: TRB, Roche, Consultancies: AbbVie, Amgen, Roche, MSD, Pfizer, Celgene, Grünenthal, Kwizda, Eli-Lilly, Novartis, Sandoz;, Peter Spellitz: None declared, Gabriela Eichbauer-Sturm: None declared, Jochen Zwerina: None declared, Manfred Herold: None declared, Miriam Stetter: None declared, Rudolf Puchner Speakers bureau: AbbVie, BMS, Janssen, Kwizda, MSD, Pfizer, Celgene, Grünenthal, Eli-Lilly, Consultant of: AbbVie, Amgen, Pfizer, Celgene, Grünenthal, Eli-Lilly, Franz Singer: None declared, Ruth Fritsch-Stork: None declared


2021 ◽  
pp. 153857442110232
Author(s):  
Spyridon N. Mylonas ◽  
Konstantinos G. Moulakakis ◽  
Nikolaos Kadoglou ◽  
Constantinos Antonopoulos ◽  
Thomas E. Kotsis ◽  
...  

Purpose: The aim of the present study was to investigate a potential difference on the arterial stiffness among aneurysm patients and non-aneurysm controls, as well as to explore potential changes between patients treated either with endovascular or open repair. Materials and Methods: A 110 patients with an infrarenal AAA were prospectively enrolled in this study. Fifty-six patients received an EVAR, whereas 54 patients received an open surgical repair. Moreover, 103 gender and age-matched subjects without AAA served as controls. The cardio-ankle vascular index (CAVI) was applied for measurement of the arterial stiffness. Results: CAVI values were statistically higher in the AAA patients when compared with control subjects. Although at 48 hours postoperatively the CAVI values were increased in both groups when compared to baseline values, the difference in CAVI had a tendency to be higher in the open group compared to the endovascular group. At 6 months of follow up the CAVI values returned to the baseline for the patients of the open repair group. However, in the endovascular group CAVI values remained higher when compared with the baseline values. Conclusion: Patients with AAAs demonstrated a higher value of CAVI compared to healthy controls. A significant increase of arterial stiffness in both groups during the immediate postoperative period was documented. The increase in arterial stiffness remained significant at 6 months in EVAR patients. Further studies are needed to elucidate the impact of a decreased aortic compliance after stentgraft implantation on the cardiac function of patients with AAA.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Projestine Selestine Muganyizi ◽  
Grasiana Festus Kimario ◽  
France John Rwegoshora ◽  
Ponsian Patrick Paul ◽  
Anita Makins

Abstract Background The insertion of Intrauterine Contraceptive Device (PPIUD) for the purpose of contraception immediately after delivery is becoming popular in countries where the use of IUD for contraception has been extremely low. Since 2015, Tanzania implemented the initiative by the International Federation of Gynecology and Obstetrics (FIGO) to institutionalize PPIUD. As a result of capacity building and information delivery under the initiative, there have been increased uptake of the method. Working in this context, the focus of the study was to generate evidence on the effect of TCu380A IUD on amount and duration of lochia and equip service providers with evidence-based knowledge which can help them in counselling their PPIUD clients. Objective Establish impact of postpartum TCu380A on amount and duration of lochia. Methods A prospective cohort study of delivered women in two teaching hospitals in Tanzania with immediate insertion of TCu380A or without use of postpartum contraception in 2018. TCu380A models; Optima (Injeflex Co. Brazil) and Pregna (Pregna International, Chakan, India) were used. Follow-up was done by weekly calls and examination at 6th week. Lochia was estimated by Likert Scale 0–4 relative to the amount of lochia on the delivery day. An estimated 250 women sample (125 each group) would give 80% power to detect a desired 20% difference in the proportion of women with prolonged lochia discharges among the Exposed and Unexposed groups. Data analysis was by SPSS. Results Two hundred sixty women were analysed, 127 Exposed and 133 Unexposed. Medical complaints were reported by 41 (28.9%) Exposed and 37 Unexposed (27.8%), p = 0.655. Lack of dryness by end of 6th week was to 31 (23.3%) Exposed and 9 (7.1%) Unexposed, p < 0.001. Exposed had higher weekly mean lochia scores throughout with the difference most marked in 5th week (3.556 Versus 2.039, p < 0.001) and 6th week (1.44 Versus 0.449, p<0.001). Conclusion PPIUD is associated with increased amount of lochia and slows progression to dryness within 6 weeks of delivery. The implications of PPIUD clients’ needs to be informed about the possibility of delayed dryness of lochia at time of counseling are discussed.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuntaro Oribe ◽  
Takafumi Toyohara ◽  
Eikan Mishima ◽  
Takehiro Suzuki ◽  
Koichi Kikuchi ◽  
...  

Abstract Background Fibromuscular dysplasia (FMD) often causes renal artery stenosis with renovascular hypertension. Recent clinical outcomes encourage percutaneous transluminal renal angioplasty (PTRA) to treat FMD; however, the necessary follow-up period remains unclear. Moreover, previous studies have not revealed the difference in the period until recurrence between two major types of FMD—multifocal and focal. Case presentation We describe two patients with multifocal FMD who developed hypertension during their teenage years and had recurrence of FMD > 10 years after PTRA. We further examined the types of FMD and age of onset in 26 patients who underwent PTRA. The period until recurrence of multifocal FMD was longer than that of focal FMD. Moreover, patients with early-onset multifocal FMD are likely to have a delayed recurrence after PTRA compared to other types. Conclusions Our report suggests that patients with multifocal FMD, especially those with onset at an early age, may need long-term follow-up for at least ≥ 10 years.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
T M Mikkola ◽  
H Kautiainen ◽  
M Mänty ◽  
M B von Bonsdorff ◽  
T Kröger ◽  
...  

Abstract Purpose Mortality appears to be lower in family caregivers than in the general population. However, there is lack of knowledge whether the difference in mortality between family caregivers and the general population is dependent on age. The purpose of this study was to analyze all-cause mortality in relation to age in family caregivers and to study their cause-specific mortality using data from multiple Finnish national registers. Methods The data included all individuals, who received family caregiver's allowance in Finland in 2012 (n = 42 256, mean age 67 years, 71% women) and a control population matched for age, sex, and municipality of residence (n = 83 618). Information on dates and causes of death between 2012 and 2017 were obtained from the Finnish Causes of Death Register. Flexible parametric survival modeling and competing risk regression adjusted for socioeconomic status were used. Results The total follow-up time was 717 877 person-years. Family caregivers had lower all-cause mortality than the controls over the follow-up (8.1% vs. 11.6%) both among women (hazard ratio [HR]: 0.64, 95% CI: 0.61-0.68) and men (HR: 0.73, 95% CI: 0.70-0.77). Younger adult caregivers had equal or only slightly lower mortality than their controls, but after age 60, the difference increased markedly resulting in over 10% lower mortality in favor of the caregivers in the oldest age groups. Caregivers had lower mortality for all the causes of death studied, namely cardiovascular, cancer, neurological, external, respiratory, gastrointestinal and dementia than the controls. Of these, the lowest was the risk for dementia (subhazard ratio=0.29, 95%CI: 0.25-0.34). Conclusions Older family caregivers have lower mortality than the age-matched controls from the general population while younger caregivers have similar mortality to their peers. This age-dependent advantage in mortality is likely to reflect selection of healthier individuals into the family caregiver role. Key messages The difference in mortality between family caregivers and the age-matched general population varies considerably with age. Advantage in mortality observed in family caregiver studies is likely to reflect the selection of healthier individuals into the caregiver role, which underestimates the adverse effects of caregiving.


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