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Jones D
; Meijer EFJ
; Blatter C
; Liao S
; Pereira ER
; Bouta EM
; Jung K
; Chin SM
; Huang P
; Munn LL
; Vakoc BJ
; Otto M
; Padera TP
Sci Transl Med
2018[Jan]; 10
(424
): ? PMID29343625
show ga
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity
and mortality worldwide and is a frequent cause of skin and soft tissue
infections (SSTIs). Lymphedema-fluid accumulation in tissue caused by impaired
lymphatic vessel function-is a strong risk factor for SSTIs. SSTIs also
frequently recur in patients and sometimes lead to acquired lymphedema. However,
the mechanism of how SSTIs can be both the consequence and the cause of lymphatic
vessel dysfunction is not known. Intravital imaging in mice revealed an acute
reduction in both lymphatic vessel contractility and lymph flow after localized
MRSA infection. Moreover, chronic lymphatic impairment is observed long after
MRSA is cleared and inflammation is resolved. Associated with decreased
collecting lymphatic vessel function was the loss and disorganization of
lymphatic muscle cells (LMCs), which are critical for lymphatic contraction. In
vitro, incubation with MRSA-conditioned supernatant led to LMC death. Proteomic
analysis identified several accessory gene regulator (agr)-controlled MRSA
exotoxins that contribute to LMC death. Infection with agr mutant MRSA resulted
in sustained lymphatic function compared to animals infected with wild-type MRSA.
Our findings suggest that agr is a promising target to preserve lymphatic vessel
function and promote immunity during SSTIs.
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