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Biofilm in group A streptococcal necrotizing soft tissue infections
Nikolai Siemens, Bhavya Chakrakodi, Srikanth Mairpady Shambat, Marina Morgan, Helena Bergsten, Ole Hyldegaard, Steinar Skrede, Per Arnell, Martin B. Madsen, Linda Johansson, INFECT Study Group, Julius Juarez, Lidija Bosnjak, Matthias Mörgelin, Mattias Svensson, Anna Norrby-Teglund
Nikolai Siemens, Bhavya Chakrakodi, Srikanth Mairpady Shambat, Marina Morgan, Helena Bergsten, Ole Hyldegaard, Steinar Skrede, Per Arnell, Martin B. Madsen, Linda Johansson, INFECT Study Group, Julius Juarez, Lidija Bosnjak, Matthias Mörgelin, Mattias Svensson, Anna Norrby-Teglund
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Research Article Infectious disease

Biofilm in group A streptococcal necrotizing soft tissue infections

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Abstract

Necrotizing fasciitis caused by group A streptococcus (GAS) is a life-threatening, rapidly progressing infection. At present, biofilm is not recognized as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is typically linked to chronic infections or associated with foreign devices. Here, we present a case of a previously healthy male presenting with NSTI caused by GAS. The infection persisted over 24 days, and the surgeon documented the presence of a “thick layer biofilm” in the fascia. Subsequent analysis of NSTI patient tissue biopsies prospectively included in a multicenter study revealed multiple areas of biofilm in 32% of the patients studied. Biopsies associated with biofilm formation were characterized by massive bacterial load, a pronounced inflammatory response, and clinical signs of more severe tissue involvement. In vitro infections of a human skin tissue model with GAS NSTI isolates also revealed multilayered fibrous biofilm structures, which were found to be under the control of the global Nra gene regulator. The finding of GAS biofilm formation in NSTIs emphasizes the urgent need for biofilm to be considered as a potential complicating microbiological feature of GAS NSTI and, consequently, emphasizes reconsideration of antibiotic treatment protocols.

Authors

Nikolai Siemens, Bhavya Chakrakodi, Srikanth Mairpady Shambat, Marina Morgan, Helena Bergsten, Ole Hyldegaard, Steinar Skrede, Per Arnell, Martin B. Madsen, Linda Johansson, INFECT Study Group, Julius Juarez, Lidija Bosnjak, Matthias Mörgelin, Mattias Svensson, Anna Norrby-Teglund

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Figure 5

SpeB, capsule, and CovR/S are not associated with biofilm formation in the tissue setting.

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SpeB, capsule, and CovR/S are not associated with biofilm formation in t...
(A) Distribution of SpeB-positive and SpeB-negative (SpeB+/SpeB–) clones recovered from biofilm- and non–biofilm-associated patient biopsies. (B) Representative immunofluorescence micrographs of the distribution of SpeB in biofilm and nonbiofilm patient biopsies (original magnification, ×40). (C) SpeB positivity among the necrotizing soft tissue infection strains used for the skin model infections (before infection and 48 hours after). (D) Western Blot analyses of secreted SpeB by indicated strains at different growth stages. Representative images of 3 experiments are shown (n = 3). (E) Relative mRNA expression of speB before and during the infection in tissue models (left panel) or in patient biopsies (right panel; stat., static culture). The data on skin tissue model (left panel) represent the mean values ± SD (n = 3). (F) Amounts of capsular hyaluronic acid in exponential growth phase bacteria. Strains from patients with biofilm-positive or -negative biopsies are shown in circles and squares, respectively. The horizontal line denotes mean values (n = 3).

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