Editorial: Microbial Biofilms in Chronic and Recurrent Infections

Biofilm plays a significant role in the pathogenesis of most chronic infections in humans, either tissue-specific or involving medical implants (Lebeaux et al., 2014). Biofilm-associated infections exhibit high resistance to host defenses, often contributing to an excessive or inappropriate inflammatory response leading to further tissue damage and spreading of the infection (Jensen et al., 2010). On the other hand, biofilms are highly tolerant to antimicrobial therapy (Römling and Balsalobre, 2012; Di Domenico et al., 2019). Biofilms can tolerate up to 100–1,000 times higher minimal inhibitory concentration (MIC) than the same bacterial cells in planktonic growth (Macià et al., 2014). Unfortunately, the effective antibiotic MIC in vivo for biofilm eradication may be impossible to reach due to the drugs’ toxicity and side effects, including limitations imposed by renal and/or hepatic functions (Ciofu et al., 2015). However, in vitro experiments showed that an aggressive antibiotic treatment can effectively eradicate biofilm during the initial stage of colonization (Lebeaux et al., 2014; Ciofu et al., 2015). Despite their importance, the early recognition of biofilm-associated infections still represents an unmet need in clinical microbiology. Therefore, the development of novel diagnostic and therapeutic strategies is urgently needed to manage biofilm-associated infections effectively

P090 Molecular epidemiology of methicillin-resistant Staphylococcus aureus in cystic fibrosis: eleven years in the life of a French cystic fibrosis centre

International audienc

Existence of a Colonizing Staphylococcus aureus Strain Isolated in Diabetic Foot Ulcers

Staphylococcus aureus is an opportunistic bacterium capable of causing a wide range of severe diseases when it gains access to underlying tissues. Paradoxically, S. aureus is a common inhabitant of the skin microflora and colonizes the nares and other human mucosa. The purpose of this study was to determine the genetic basis for the differences in the pathogenic versus colonizing potential of S. aureus isolated from diabetic foot ulcers (DFUs). By performing optical map comparisons of a collection of S. aureus strains isolated from DFUs, we brought to light a prophage present in noninfecting bacteria. The phage, namely ROSA-like, was localized in a hotspot region ΦNM2 near the locus isd, the iron surface determinant system. The integrated phage significantly reduces the virulence of the strain and increases the biofilm formation. DFUs seem to be a specific niche of this colonizing strain. The ROSA-like phage represents the first description of a mobile element present mainly in S. aureus isolated from DFUs, which modulates the relationship of the bacteria with its human host. This phage appears to attenuate bacterial virulence and promote colonization

Expression of chemokine receptors by Th17 cells during primary HIV infection.

<p>Th1 and Th17 cells were assessed after 5 h PMA/ionomycin stimulation of fresh isolated CD4 T cells and defined by the expression of IFN-γ and IL-2 (Th1) or IL-17 (Th17). In each datasets, horizontal lines indicate the medians. Panels A-D show results at baseline; panel E illustrates both baseline and month 6 measurements. (Panel A) Frequency of CCR4, CCR6 and CXCR3 among bulk CD4 T cells, Th1 cells and Th17 cells. (Panel B) Correlation between the proportion of CCR6 expressing CD4 T cells and the Th17 frequency. Spearman's rank correlation coefficients ‘R’ and corresponding p values are indicated. (Panel C) Expression of CCR4, CCR6 and CXCR3 among Th17 cells in patients with high (>median) and low (</p

Patients' characteristics.

<p>Data are expressed as median (IQR).</p>*<p>For one patient experiencing an intercurrent episode associated with high level of inflammation at M6, clinical data from M3 were used.</p>**<p>Twelve patients received ART between baseline and M6. Two patients were lost to follow-up.</p

Intestinal mucosal integrity and microbial translocation markers during primary HIV infection.

<p>Plasma levels of I-FABP (Panel A) and plasma EndoCAb IgM levels (Panel B) were measured in PHI patients at baseline and month 6 and in healthy donors. Purple lines indicate patients receiving antiretroviral therapy between baseline and month 6; grey lines indicate untreated patients. Mann-Whitney tests were performed to compare patients and healthy donors, Wilcoxon rank tests was used to compared baseline and month 6 values in all patients; significant p values are indicated. (Panel C) Number of patients with detectable peptidoglycans in plasma using SLP reagents. (Panel D) Plasma levels of 16S ribosomal DNA in PHI patients at baseline (n = 27) and month 6 (n = 25), in untreated chronically HIV-infected patients (n = 20) as well as in patients with sepsis and blood culture positive for <i>Staphylococcus aureus</i> (n = 10).</p

Longitudinal follow-up of CD8 T-cell activation, CD4 cell counts and of plasma HIV-RNA levels in patients with primary HIV infection.

<p>At baseline (Panel A), frequencies of CD38⁺HLA-DR⁺ CD8 T cells were compared in patients that remained untreated during the 6-month follow-up (n = 13, Untreated) and in patients that have been subsequently treated before M6 (n = 12, Subsequently treated). CD8 T-cell activation was longitudinally assessed in untreated patients (n = 13) by measuring the frequency of CD38⁺HLA-DR⁺ cells (Panel B) and of Ki-67⁺ cells (Panel C) among CD8⁺ T cells at baseline, day 15 (D15), month 1 (M1), month 3 (M3) and month 6 (M6). Panel D illustrates the proportion of CD38⁺HLA-DR⁺ cells among CD8 T cells in untreated patients, in ART-treated patients at M6 and in healthy controls (n = 14). CD4 T cell counts (Panel E) and plasma HIV-1 RNA levels (Panel F) were plotted as a function of time during the 6 months of follow-up in treated (blue lines) and untreated (red lines) patients. Data are expressed as mean ± SEM. Wilcoxon rank tests were performed and p values are indicated between indicated time points for untreated patients (Panels B, C, E, F). Mann-Whitney tests were performed to compare groups of patients (Panels A and D).</p

The Th17/Treg ratio and monocyte activation markers at baseline predict the T-cell activation set point.

<p>Panels depict the relationships between the Th17/Treg ratio (Panel A), plasma levels of sCD14 (Panel B) or IL-1RA (C) at baseline and CD8 T cell activation at month 6. The T-cell activation set point was defined as the frequency of CD8 T cells co-expressing CD38 and HLA-DR or expressing Ki-67 at month 6. Spearman's rank correlation coefficients ‘R’ and corresponding p values are indicated on each panel.</p