M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of &lt;i&gt;Streptococcus pyogenes&lt;/i&gt; in Macrophages

Hertzén, Erika; Johansson, Linda; Wallin, Robert P. A.; Schmidt, Hannes; Kroll, Mirko; Rehn, Anders; Kotb, Malak; Mörgelin, Matthias; Norrby‐Teglund, Anna

doi:10.1159/000317635

Cited by 55 publications

(90 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Isolation of monocytes was performed essentially as previously described (31,32). In brief, CD14 ϩ monocytes were isolated from buffy coats by negative selection using RosetteSep human monocyte enrichment cocktail (0.5 ml/10 ml blood; StemCell Technologies, Vancouver, Canada) and separated on Ficoll-Paque Plus.…”

Section: Methodsmentioning

confidence: 99%

Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection

Eriksson

Geörg

Sjölinder

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bMeningococcal disease is characterized by a fast progression and a high mortality rate. Cell-penetrating peptides (CPPs), developed as vectors for cargo delivery into eukaryotic cells, share structural features with antimicrobial peptides. A screen identified two CPPs, transportan-10 (TP10) and model amphipathic peptide (MAP), with bactericidal action against Neisseria meningitidis. Both peptides were active in human whole blood at micromolar concentrations, while hemolysis remained negligible. Additionally, TP10 exhibited significant antibacterial activity in vivo. Uptake of SYTOX green into live meningococci was observed within minutes after TP10 treatment, suggesting that TP10 may act by membrane permeabilization. Apart from its bactericidal activity, TP10 suppressed inflammatory cytokine release from macrophages infected with N. meningitidis as well as from macrophages stimulated with enterobacterial and meningococcal lipopolysaccharide (LPS). Finally, incubation with TP10 reduced the binding of LPS to macrophages. This novel endotoxin-inhibiting property of TP10, together with its antimicrobial activity in vivo, indicates the possibility to design peptide-based therapies for infectious diseases.

show abstract

Section: Methodsmentioning

confidence: 99%

Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection

Eriksson

Geörg

Sjölinder

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Co gorsze, bakterie mają-ce na swojej powierzchni ekspresję białka M1 wykazują zdolność do unikania połączeń z lizozymami wewnątrz makrofagów. Powoduje to stan, w którym makrofagi stanowią nie tylko bezpieczny rezerwuar pozwalający przetrwać paciorkowcom, ale dochodzi w nich wręcz do replikacji bakterii [15]. Jest to szczególnie niebezpieczne zjawisko będące podstawą patogenności i zdolności wywołania wstrząsu septycznego.…”

Section: Dyskusjaunclassified

Necrotizing fasciitis after Caesarean section. Can this complication be avoided?

Raba¹

2013

View full text Add to dashboard Cite

StreszczenieMartwicze zapalenie powięzi (MZP) to rodzaj ostrego zakażenia podskórnej tkanki łącznej, które szerzy się wzdłuż powięzi okrywających mięśnie. Prowadzi do zespołu wstrząsu toksycznego oraz wysokiej śmiertelności. Osoby, które przeżyły, cierpią często z powodu powikłań. Do najczęstszych zalicza się: inne zakażenia szpitalne (76%), zespoły niewydolności oddechowej (29%) oraz ostrą niewydolność nerek (32%). Najczęstszym czynnikiem etiologicznym MZP jest Streptococcus pyogenes, samodzielnie albo łącznie z innymi patogenami. W celu zmniejszenia ryzyka wystąpienia zakażeń wywoływanych przez paciorkowce większość towarzystw ginekologiczno-położniczych rekomenduje profilaktyczne pobieranie posiewów bakteriologicznych u kobiet ciężarnych w okresie przedporodowym i stosowanie profilaktycznej antybiotykoterapii przedporodowej u nosicielek. Jednak nie pozwala to na całkowite uniknięcie ryzyka choroby. Współcześnie w dobie masowego nadużywania antybiotyków w różnych dziedzinach medycyny liczba szczepów paciorkowców wykazujących ekspresję białka M1 wzrasta. Równocześnie obserwuje się wzrost odsetka wykonywanych cięć cesarskich. Nasuwa to obawy przed wzrostem częstości występowania MZP po cięciach cesarskich. Głównym czynnikiem poprawiającym rokowanie w przebiegu MZP po cięciu cesarskim jest wczesna interwencja chirurgiczna. Znajomość przebiegu klinicznego MZP powinna zwiększać trafność dokonywanych rozpoznań i przyspieszać wdrażanie agresywnego leczenia chirurgicznego oraz intensywnej antybiotykoterapii, znacznie zmniejszając śmiertelność związaną z chorobą.Słowa kluczowe: martwicze zapalenie powięzi, cięcie cesarskie, ciąża. SummaryNecrotizing fasciitis (NF) is a type of acute infection of the subcutaneous connective tissue, which spreads along the fasciae surrounding the muscles. It leads to the toxic shock syndrome and a high mortality rate. Survivors often suffer from complications, of which the most common include other hospital-acquired infections (76%), respiratory failure syndromes (29%) and acute renal failure (32%). The most common etiological agent of NF is Streptococcus pyogenes, alone or in combination with other pathogens. To reduce the risk of infections caused by Streptococci, most gynaecological and obstetric institutions recommend that pregnant women take bacteriological cultures prophylactically in the prenatal period and that prophylactic prenatal antibiotic therapy be administered to carriers. However this does not enable the risk of the disease to be eliminated completely. At present, when antibiotics are widely overused in various branches of medicine, there is an increase in the number of Streptococci strains expressing the M1 protein. A rise can also be observed in the percentage of Caesarean deliveries. This raises concerns about an increase in the frequency of NF following Caesarean sections. The main factor improving the prognosis for NF following a Caesarean section is an early surgical intervention. Knowledge of the clinical course of NF can be expected to increase the accuracy of dia...

show abstract

“…Although S. pyogenes has been considered as an extracellular pathogen, various reports have shown that it invades different cell types in vitro including epithelial cells [4,5,6], neutrophils [7,8] and macrophages [9,10]. Internalization of S. pyogenes into eukaryotic cells is considered to be one successful mechanism for evading host immune responses and penicillin treatment, and it may thus promote transmission and dissemination from the primary side of infection.…”

Section: Introductionmentioning

confidence: 99%

The M1 Protein of <b><i>Streptococcus pyogenes</i></b> Triggers an Innate Uptake Mechanism into Polarized Human Endothelial Cells

Ochel

Rohde²,

Chhatwal³

et al. 2014

J Innate Immun

View full text Add to dashboard Cite

Serotype M1 Streptococcus pyogenes is a major human pathogen associated with severe invasive diseases causing high morbidity and mortality. In a substantial number of cases, invasive disease develops in previously healthy individuals with no obvious port of entry. This has led to the hypothesis that the source of streptococci in these cases is a transient bacteraemia. This study focuses on the analysis of interaction of tissue-invasive serotype M1 S. pyogenes with human endothelial cells (EC) of the vascular system. We identify the M1 surface protein of S. pyogenes as the EC invasin which is recognised by polarized human blood EC, thereby triggering rapid, phagocytosis-like uptake of streptococci into polarized EC layers. Upon internalization, the M1 S. pyogenes serotype is incorporated into phagosomes which traffic via the endosomal/lysosomal pathway. However, some of the streptococci successfully evade this innate killing process and hereby mediate their escape into the cytoplasm of the host cell. The results of this study demonstrate that blood EC possess an efficient uptake mechanism for serotype M1 S. pyogenes. Despite efficient phagocytosis, streptococcal survival within EC constitutes one potential mechanism which favours intracellular persistence and thus facilitates continuous infection and dissemination from the primary side of infection into deep tissue.

show abstract

M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of <i>Streptococcus pyogenes</i> in Macrophages

Cited by 55 publications

References 77 publications

Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection

Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection

Necrotizing fasciitis after Caesarean section. Can this complication be avoided?

The M1 Protein of <b><i>Streptococcus pyogenes</i></b> Triggers an Innate Uptake Mechanism into Polarized Human Endothelial Cells

Contact Info

Product

Resources

About