Skin Microbiome in Atopic Dermatitis Edslev, Sofie M; Agner, Tove; Andersen, Paal S
Acta dermato-venereologica,
06/2020, Letnik:
100, Številka:
12
Journal Article
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Atopic dermatitis is a common inflammatory skin disease with a complex pathogenesis that includes imbalanced immune system signalling, impaired skin barrier and enhanced Staphylococcus aureus skin ...colonization. The skin bacterial communities are characterized by increasing abundance of S. aureus, leading to reduced diversity compared with the bacterial communities on healthy skin, and increasing disease severity. In contrast, fungal communities are richer and more diverse on the skin of patients with atopic dermatitis, although distribution of the most common species is similar in patients and controls. Filaggrin deficiency in atopic dermatitis skin might be related to the enhanced skin colonization by S. aureus. In addition, S. aureus expressing variant virulence factors have been shown to elicit atopic dermatitis-like phenotypes in mice, indicating that specific S. aureus strains can induce flare-ups. This review aims to provide an overview of the recent literature on the skin microbiome in atopic dermatitis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Highly invasive, community-acquired Klebsiella pneumoniae infections have recently emerged, resulting in pyogenic liver abscesses. These infections are caused by hypervirulent K. pneumoniae (hvKP) ...isolates primarily of capsule serotype K1 or K2. Hypervirulent K1 isolates belong to clonal complex 23 (CC23), indicating that this clonal lineage has a specific genetic background conferring hypervirulence. Here, we apply whole-genome sequencing to a collection of K. pneumoniae isolates to characterize the phylogenetic background of hvKP isolates with an emphasis on CC23. Most of the hvKP isolates belonged to CC23 and grouped into a distinct monophyletic clade, revealing that CC23 is a unique clonal lineage, clearly distinct from nonhypervirulent strains. Separate phylogenetic analyses of the CC23 isolates indicated that the CC23 lineage evolved recently by clonal expansion from a single common ancestor. Limited grouping according to geographical origin was observed, suggesting that CC23 has spread globally through multiple international transmissions. Conversely, hypervirulent K2 strains clustered in genetically unrelated groups. Strikingly, homologues of a large virulence plasmid were detected in all hvKP clonal lineages, indicating a key role in K. pneumoniae hypervirulence. The plasmid encodes two siderophores, aerobactin and salmochelin, and RmpA (regulator of the mucoid phenotype); all these factors were found to be restricted to hvKP isolates. Genomic comparisons revealed additional factors specifically associated with CC23. These included a distinct variant of a genomic island encoding yersiniabactin, colibactin, and microcin E492. Furthermore, additional novel genomic regions unique to CC23 were revealed which may also be involved in the increased virulence of this important clonal lineage.
During the last 3 decades, hypervirulent Klebsiella pneumoniae (hvKP) isolates have emerged, causing severe community-acquired infections primarily in the form of pyogenic liver abscesses. This syndrome has so far primarily been found in Southeast Asia, but increasing numbers of cases are being reported worldwide, indicating that the syndrome is turning into a globally emerging disease. We applied whole-genome sequencing to a collection of K. pneumoniae clinical isolates to reveal the phylogenetic background of hvKP and to identify genetic factors associated with the increased virulence. The hvKP isolates primarily belonged to clonal complex 23 (CC23), and this clonal lineage was revealed to be clearly distinct from nonhypervirulent strains. A specific virulence plasmid was found to be associated with hypervirulence, and novel genetic determinants uniquely associated with CC23 were identified. Our findings extend the understanding of the genetic background of the emergence of hvKP clones.
We report a fatal aspergillosis case in which STRAf typing and whole-genome sequencing substantiated in vivo emergence of an azole-resistant Aspergillus fumigatus with a 120-bp tandem repeat in the ...promoter region of cyp51A. This event, previously restricted to the environment, challenges current understanding of azole resistance development in A. fumigatus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives: A microbiotic profile characterized by decreased abundance and richness has been described in inflammatory bowel disease (IBD). Recently, sequencing the microbiome to the species level ...has become possible, which can improve our understanding of the gut to host interaction in IBD. We aimed to describe the microbiotic profile in paediatric IBD and compare it to disease phenotype and disease course.
Methods: Faecal samples were collected from a cross-sectional cohort. The microbiome analysis was performed using 16S and 18S rRNA sequencing with the miSeq instrument. Inflammatory activity was assessed by faecal calprotectin. Data regarding medical treatment and surgery in the year after faecal sampling were collected from patient charts.
Results: One hundred and forty-three (143) paediatric IBD patients and 34 healthy controls (HC) were included. We found a reduced richness in IBD patients compared to HCs (controls vs. ulcerative colitis (UC), p < .001 and controls vs. Crohn's disease (CD), p = .04)). Moreover, a high degree of intestinal inflammation and extensive disease extent was associated with reduced richness in UC (p = .02 and p = .04, respectively). Nine species were significantly associated with a healthy microbiome and three species were associated with IBD. Lastly, we found that the composition of the microbiome could distinguish between CD, UC and HCs.
Conclusions: In this study, we found that the microbiome could discriminate between IBD phenotypes and predict which patients were at risk of surgery. In the future, this could be included as part of the diagnostic work-up in IBD patients.
Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers,
is an opportunistic pathogen capable of causing severe infections.
virulence is controlled by the
...quorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase.
loci are found also in other staphylococcal species and for
, the encoded AIP represses expression of
regulated virulence genes in
. In this study we aimed to better understand the interaction between staphylococci and
, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target
infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit
. The dog pathogen,
, expressed the most potent inhibitory activity and was active against all four
classes found in
. By employing a
strain encoding a constitutively active AIP receptor we show that the activity is mediated via
. Subsequent cloning and heterologous expression of the
AIP in
demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic
AIP was able to completely abolish
induction of an
reporter strain. To assess impact on
virulence, we co-inoculated
and
in the
wax moth larva, and found that expression of key
virulence factors was abrogated. Our data show that the
locus is highly responsive to other staphylococcal species suggesting that
is an inter-species communication system. Based on these results we speculate that interactions between
and other colonizing staphylococci will significantly influence the ability of
to cause infection, and we propose that other staphylococci are potential sources of compounds that can be applied as anti-virulence therapy for combating
infections.
The Escherichia coli sequence type 131 (ST131) clone is notorious for extraintestinal infections, fluoroquinolone resistance, and extended-spectrum beta-lactamase (ESBL) production, attributable to a ...CTX-M-15-encoding mobile element. Here, we applied pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing to reconstruct the evolutionary history of the ST131 clone. PFGE-based cluster analyses suggested that both fluoroquinolone resistance and ESBL production had been acquired by multiple ST131 sublineages through independent genetic events. In contrast, the more robust whole-genome-sequence-based phylogenomic analysis revealed that fluoroquinolone resistance was confined almost entirely to a single, rapidly expanding ST131 subclone, designated H30-R. Strikingly, 91% of the CTX-M-15-producing isolates also belonged to a single, well-defined clade nested within H30-R, which was named H30-Rx due to its more extensive resistance. Despite its tight clonal relationship with H30Rx, the CTX-M-15 mobile element was inserted variably in plasmid and chromosomal locations within the H30-Rx genome. Screening of a large collection of recent clinical E. coli isolates both confirmed the global clonal expansion of H30-Rx and revealed its disproportionate association with sepsis (relative risk, 7.5; P < 0.001). Together, these results suggest that the high prevalence of CTX-M-15 production among ST131 isolates is due primarily to the expansion of a single, highly virulent subclone, H30-Rx.
We applied an advanced genomic approach to study the recent evolutionary history of one of the most important Escherichia coli strains in circulation today. This strain, called sequence type 131 (ST131), causes multidrug-resistant bladder, kidney, and bloodstream infections around the world. The rising prevalence of antibiotic resistance in E. coli is making these infections more difficult to treat and is leading to increased mortality. Past studies suggested that many different ST131 strains gained resistance to extended-spectrum cephalosporins independently. In contrast, our research indicates that most extended-spectrum-cephalosporin-resistant ST131 strains belong to a single highly pathogenic subclone, called H30-Rx. The clonal nature of H30-Rx may provide opportunities for vaccine or transmission prevention-based control strategies, which could gain importance as H30-Rx and other extraintestinal pathogenic E. coli subclones become resistant to our best antibiotics.
Staphylococcus aureus
is a commensal colonizer of both humans and animals, but also an opportunistic pathogen responsible for a multitude of diseases. In recent years, colonization of pigs by ...methicillin resistant
S. aureus
has become a problem with increasing numbers of humans being infected by livestock strains. In
S. aureus
colonization and virulence factor expression is controlled by the
agr
quorum sensing system, which responds to and is activated by self-generated, autoinducing peptides (AIPs). AIPs are also produced by coagulase negative staphylococci (CoNS) commonly found as commensals in both humans and animals, and interestingly, some of these inhibit
S. aureus agr
activity. Here, we have addressed if cross-communication occurs between
S. aureus
and CoNS strains isolated from pig nares, and if so, how properties such as host factor binding and biofilm formation are affected. From 25 pig nasal swabs we obtained 54 staphylococcal CoNS isolates belonging to 8 different species. Of these, none were able to induce
S. aureus agr
as monitored by reporter gene fusions to
agr
regulated genes but a number of
agr
-inhibiting species were identified including
Staphylococcus hyicus
,
Staphylococcus simulans
,
Staphylococcus arlettae
,
Staphylococcus lentus
, and
Staphylococcus chromogenes
. After establishing that the inhibitory activity was mediated via AgrC, the receptor of AIPs, we synthesized selective AIPs to explore their effect on adhesion of
S. aureus
to fibronectin, a host factor involved in
S. aureus
colonization. Here, we found that the CoNS AIPs did not affect adhesion of
S. aureus
except for strain 8325-4. When individual CoNS strains were co-cultured together with
S. aureus
we observed variable degrees of biofilm formation which did not correlate with
agr
interactions. Our results show that multiple CoNS species can be isolated from pig nares and that the majority of these produce AIPs that inhibit
S. aureus agr
. Further they show that the consequences of the interactions between CoNS and
S. aureus
are complex and highly strain dependent.
Staphylococcus aureus clonal complex 398 (CC398) isolates cluster into two distinct phylogenetic clades based on single-nucleotide polymorphisms (SNPs) revealing a basal human clade and a more ...derived livestock clade. The scn and tet(M) genes are strongly associated with the human and the livestock clade, respectively, due to loss and acquisition of mobile genetic elements. We present canonical single-nucleotide polymorphism (canSNP) assays that differentiate the two major host-associated S. aureus CC398 clades and a duplex PCR assay for detection of scn and tet(M). The canSNP assays correctly placed 88 S. aureus CC398 isolates from a reference collection into the human and livestock clades and the duplex PCR assay correctly identified scn and tet(M). The assays were successfully applied to a geographically diverse collection of 272 human S. aureus CC398 isolates. The simple assays described here generate signals comparable to a whole-genome phylogeny for major clade assignment and are easily integrated into S. aureus CC398 surveillance programs and epidemiological studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of ...clinical screening and predictive genetic testing of child relatives of patients with HCM.
Ninety probands and 361 relatives were included in a family screening program for HCM (1994-2001). Eleven sarcomere genes, CRYAB, α-GAL, and titin were screened. Sixty-six relatives and 4 probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2-18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact.
The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years of follow-up. The finding of phenotype conversion in the mid-20s warrants continued screening into adulthood. Forty-two percent of the child relatives were noncarriers, and repeat clinical follow-up could be safely limited to the remaining children.
Cathelicidin (LL-37) and human β-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important ...for developing uncomplicated Escherichia coli urinary tract infections (UTIs). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 and in vivo virulence. Forty-seven UTI patients and 50 controls who had never had a UTI were included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecal E. coli clones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D). In vivo virulence was investigated in the murine UTI model by use of selected fecal isolates from patients and controls. On average, UTI patients had significantly more LL-37 in urine during infection than postinfection, and patient LL-37 levels postinfection were significantly lower than those of controls. hBD-1 showed similar urine levels for UTI patients and controls. Fecal E. coli isolates from controls had higher LL-37 susceptibility than fecal and UTI E. coli isolates from UTI patients. In vivo studies showed a high level of virulence of fecal E. coli isolates from both patients and controls and showed no difference in virulence correlated with the LL-37 MIC level. The results indicate that the concentration of LL-37 in the urinary tract and low susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay between host and pathogen attributes.
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