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| 2. |
- Chamoun, Sherley, et al.
(författare)
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Colistin Dependence in Extensively Drug-Resistant Acinetobacter baumannii Strain Is Associated with ISAjo2 and ISAba13 Insertions and Multiple Cellular Responses
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:2
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Tidskriftsartikel (refereegranskat)abstract
- The nosocomial opportunistic Gram-negative bacterial pathogen Acinetobacter baumannii is resistant to multiple antimicrobial agents and an emerging global health problem. The polymyxin antibiotic colistin, targeting the negatively charged lipid A component of the lipopolysaccharide on the bacterial cell surface, is often considered as the last-resort treatment, but resistance to colistin is unfortunately increasing worldwide. Notably, colistin-susceptible A. baumannii can also develop a colistin dependence after exposure to this drug in vitro. Colistin dependence might represent a stepping stone to resistance also in vivo. However, the mechanisms are far from clear. To address this issue, we combined proteogenomics, high-resolution microscopy, and lipid profiling to characterize and compare A. baumannii colistin-susceptible clinical isolate (Ab-S) of to its colistin-dependent subpopulation (Ab-D) obtained after subsequent passages in moderate colistin concentrations. Incidentally, in the colistin-dependent subpopulation the lpxA gene was disrupted by insertion of ISAjo2, the lipid A biosynthesis terminated, and Ab-D cells displayed a lipooligosaccharide (LOS)-deficient phenotype. Moreover, both mlaD and pldA genes were perturbed by insertions of ISAjo2 and ISAba13, and LOS-deficient bacteria displayed a capsule with decreased thickness as well as other surface imperfections. The major changes in relative protein abundance levels were detected in type 6 secretion system (T6SS) components, the resistance-nodulation-division (RND)-type efflux pumps, and in proteins involved in maintenance of outer membrane asymmetry. These findings suggest that colistin dependence in A. baumannii involves an ensemble of mechanisms seen in resistance development and accompanied by complex cellular events related to insertional sequences (ISs)-triggered LOS-deficiency. To our knowledge, this is the first study demonstrating the involvement of ISAjo2 and ISAba13 IS elements in the modulation of the lipid A biosynthesis and associated development of dependence on colistin.
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| 3. |
- Claesson, Carina, et al.
(författare)
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Antimicrobial activity of tigecycline and comparative agents against clinical isolates of staphylococci and enterococci from ICUs and general hospital wards at three Swedish university hospitals
- 2009
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Ingår i: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 41:3, s. 171-181
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Tidskriftsartikel (refereegranskat)abstract
- The activities of tigecycline and comparative agents on staphylococci and enterococci isolated from patients at general hospital wards (GHWs) and intensive care units (ICUs) at 3 university hospitals in Sweden were investigated. Oxacillin disc diffusion and minimal inhibitory concentration with E-test were used. The presence of mecA, vanA or vanB genes was determined with PCR. Statistically significant higher incidence of clindamycin, fusidic acid, rifampicin and multidrug-resistant CoNS was found at ICUs compared to GHWs. Resistance rates were low among S. aureus. Tigecycline, linezolid and vancomycin were the only agents with high activity against methicillin-resistant S. aureus and multidrug-resistant CoNS. Resistance rates were low among E. faecalis, except for high-level gentamicin-resistant (HLGR) E. faecalis. E. faecium showed high resistance rates to ampicillin, piperacillin/tazobactam and imipenem. The HLGR rates among E. faecium were lower than the rates for E. faecalis. Tigecycline and linezolid were the only drugs with high activity against all enterococci including vancomycin-resistant enterococci. No statistically significant differences in susceptibility rates were found between the ward levels for S. aureus and enterococcal isolates and no statistically significant differences were found between the hospitals.
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| 4. |
- Claesson, Carina, 1970-, et al.
(författare)
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Molecular typing and detection of the aap and atlE genes and ica operon in multi-drug resistant and susceptible coagulase negative staphylococci
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the present study were to identify clinical isolates of multidrug resistant (MDR) and susceptible coagulase negative staphylococci (CoNS), (n=76) to the species level by rpoB amplicon sequencing and to detect and compare the presence of the atlE and aap genes and the ica operon between MDR (n=26) and susceptible (n=27) Staphylococcus epidermidis isolates. Detection of the atlE and aap genes and ica operon was carried out using PCR amplification. Most of the isolates were S. epidermidis, both among the MDR and susceptible CoNS. Staphylococcus haemolyticus was the only other species found in the MDR group. All MDR and 96% of the susceptible S. epidermidis isolates carried the atlE gene. The ica operon was present in about 30% of both the MDR and susceptible S. epidermidis isolates. By comparison, aap gene carriage was more common among susceptible S. epidermidis isolates (44%) than the MDR S. epidermidis isolates (27%). The atlE gene was the only gene that was found alone in the S. epidermidis genome. About 25% of the S. epidermidis isolates carried the atlE and aap genes and the ica operon simultaneously. In conclusion, rpoB gene amplicon sequencing is an easy and reliable method to identify CoNS isolates at the species and subspecies level. Both MDR and susceptible S. epidermidis isolates were found to be well equipped with adhesion and aggregation genes which might help them to adhere to artificial surfaces, colonize hospitalised patients and cause biofilm-related infections.
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| 5. |
- Claesson, Carina, 1970-
(författare)
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Staphylococci and Enterococci : Studies on activity of antimicrobial agents and detection of genes involved in biofilm formation
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Gram-positive cocci, Staphylococcus aureus, coagulase negative staphylococci (CoNS), Enterococcus faecalis and Enterococcus faecium, are the bacteria most often isolated from patients with hospital acquired infections. S. aureus is one of the most important pathogens and have a variety of virulence mechanisms which help it to infect the patient and cause tissue damage. CoNS and enterococci are low virulent bacteria and predominantly cause infections in individuals with underlying illness, individuals that have undergone surgery or with suppressed immune-system. The aims of this thesis were i) to investigate the susceptibility to different antimicrobial agents among S. aureus, CoNS, E. faecium and E. faecalis isolates from primary care centres, general hospital wards and intensive care units in Denmark, Finland, Norway and Sweden and ii) to study the prevalence of the cytolysin genes and genes involved in biofilm formation among CoNS, E. faecium and E. faecalis. The results in this thesis show that the resistance rates among S. aureus and E. faecalis is still rather low in the north European countries. Among CoNS and E. faecium resistance rates are higher and comparable with rates in other European countries and US. CoNS had statistically significant differences in susceptibility rates between the ward levels with the lower susceptibility rates found at ICUs. Continued surveillance of resistance rates to antimicrobial agents among both staphylococci and enterococci are important internationally, nationally and locally. The results in this thesis also show that all multidrug resistant and 96% of the susceptible CoNS isolates carried at least one of the atlE and aap genes or the ica operon. Among E. faecalis isolates with HLGR, belonging to a cluster of genetically related isolates, both the esp and asa1 genes were carried in a high degree while the cyl operon was less frequently found. In addition, about 30% of unique E. faecalis isolates carried two or more of the virulence genes. Among E. faecium isolates the esp gene was common but asa1 and the cyl operon was not found in any of the isolates. Both CoNS and E. faecalis isolates from hospitalised patients are well equipped with genes involved in biofilm formation. These genes, when expressed and even more in combination with resistance to antimicrobial agents, might give these isolates an advantage compared to other isolates when it comes to adhesion to artificial surfaces, persistence in the hospital environment, colonisation of hospitalised patients and to cause nosocomial infections. Further studies are needed to be able to determine which isolates that causes hospital acquired infections and to evaluate the importance of the genes involved in biofilm formation as virulence factors and about how to prevent biofilm related infections from emerging
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| 6. |
- Claesson, Carina, 1970-, et al.
(författare)
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Susceptibility of staphylococci and enterococci to antimicrobial agents at different ward levels in four north European countries
- 2007
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:11-12, s. 1002-1012
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Tidskriftsartikel (refereegranskat)abstract
- A multicentre susceptibility study was performed on staphylococci and enterococci isolated from patients at 3 different ward levels: primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs), in Denmark, Finland, Norway and Sweden. There was a markedly higher incidence of resistance among CoNS in ICUs compared to GHWs and PCCs. Resistance rates were low among S. aureus isolates and no differences were found between the ward levels. Oxacillin resistance was found among 1.6% of S. aureus and 47% of CoNS isolates. 14% of CoNS and 0.9% of S. aureus isolates were glycopeptide intermediate. The prevalence of E. faecium isolates in this study differed significantly between the ward levels with the lowest prevalence found at PCCs. High level gentamicin resistant (HLGR) enterococci occurred in 11-25% of E. faecium and 6-20% of E. faecalis isolates. The HLGR rate was significantly higher among E. faecalis from hospitalized patients (GHWs and ICUs) compared to patients at PCCs. For enterococcal isolates, no other significant differences in antimicrobial resistance were found between the ward levels. All enterococci were teicoplanin susceptible, but decreased susceptibility to vancomycin was found among 2.0% and 0.6% of the E. faecium and E. faecalis isolates, respectively.
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| 7. |
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| 8. |
- Dellgren, Linus, et al.
(författare)
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Phenotypic screening for quinolone resistance in Escherichia coli
- 2019
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : SPRINGER. - 0934-9723 .- 1435-4373. ; 38:9, s. 1765-1771
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies show that rectal colonization with low-level ciprofloxacin-resistant Escherichia coli (ciprofloxacin minimal inhibitory concentration (MIC) above the epidemiological cutoff point, but below the clinical breakpoint for resistance), i.e., in the range amp;gt; 0.06-0.5 mg/L is an independent risk factor for febrile urinary tract infection after transrectal ultrasound-guided biopsy (TRUS-B) of the prostate, adding to the other risk posed by established ciprofloxacin resistance in E. coli (MIC amp;gt; 0.5 mg/L) as currently defined. We aimed to identify the quinolone that by disk diffusion best discriminates phenotypic wild-type isolates (ciprofloxacin MIC amp;lt;= 0.06 mg/L) of E. coli from isolates with acquired resistance, and to determine the resistance genotype of each isolate. The susceptibility of 108 E. coli isolates was evaluated by ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, and pefloxacin disk diffusion and correlated to ciprofloxacin MIC (broth microdilution) using EUCAST methodology. Genotypic resistance was identified by PCR and DNA sequencing. The specificity was 100% for all quinolone disks. Sensitivity varied substantially, as follows: ciprofloxacin 59%, levofloxacin 46%, moxifloxacin 59%, nalidixic acid 97%, and pefloxacin 97%. We suggest that in situations where low-level quinolone resistance might be of importance, such as when screening for quinolone resistance in fecal samples pre-TRUS-B, a pefloxacin (S amp;gt;= 24 mm) or nalidixic acid (S amp;gt;= 19 mm) disk, or a combination of the two, should be used. In a setting where plasmid-mediated resistance is prevalent, pefloxacin might perform better than nalidixic acid.
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| 9. |
- Hayashi, Makoto, et al.
(författare)
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VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 1672-
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endothelium-specific vascular endothelial-phosphotyrosine phosphatase (VE-PTP). VE-PTP acts on VEGF receptor-2 located in endothelial junctions indirectly, via the Angiopoietin-1 receptor Tie2. VE-PTP inactivation in mouse embryoid bodies leads to excess VEGF receptor-2 activity in stalk cells, increased tyrosine phosphorylation of VE-cadherin and loss of cell polarity and lumen formation. Vessels in ve-ptp(-/-) teratomas also show increased VEGF receptor-2 activity and loss of endothelial polarization. Moreover, the zebrafish VE-PTP orthologue ptp-rb is essential for polarization and lumen formation in intersomitic vessels. We conclude that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGF receptor-2 activity regulates VE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation.
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| 10. |
- Holgerson, Pernilla L, et al.
(författare)
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Oral microbial profile discriminates breast-fed from formula-fed infants
- 2013
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 56:2, s. 127-136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Little is known about the effect of diet on the oral microbiota of infants, although diet is known to affect the gut microbiota. The aims of the present study were to compare the oral microbiota in breast-fed and formula-fed infants, and investigate growth inhibition of streptococci by infant-isolated lactobacilli.Methods: A total of 207 mothers consented to participation of their 3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38 (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva from all of their infants was cultured for Lactobacillus species, with isolate identifications from 21 infants. Lactobacillus isolates were tested for their ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73 infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM) and by quantitative polymerase chain reaction for Lactobacillus gasseri.Results: Lactobacilli were cultured from 27.8% of exclusively and partially breast-fed infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected taxa, and total salivary lactobacilli counts differed by feeding method. Multivariate modelling of HOMIM-detected bacteria and possible confounders clustered samples from breast-fed infants separately from formula-fed infants. The microbiota of breast-fed infants differed based on vaginal or C-section delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L vaginalis.Conclusions: The microbiota of the mouth differs between 3-month-old breast-fed and formula-fed infants. Possible mechanisms for microbial differences observed include species suppression by lactobacilli indigenous to breast milk.
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