Pneumonia caused by Acinetobacter baumannii has become a serious threat to the elderly. However, there are no experimental studies on the relevance between aging and A. baumannii infections. Here, we established an aged pneumonia mouse model by non-invasive intratracheal inoculation with A. baumannii. Higher mortality was observed in aged mice along with increased bacterial burdens and more severe lung injury. Increased inflammatory cell infiltration and enhanced pro-inflammatory cytokines at 24 hours post infection were detected in aged mice than those in young mice. Moreover, infected aged mice had lower myeloperoxidase levels in lungs and less reactive oxygen species-positive neutrophils in bronchoalveolar lavage fluid compared with infected young mice. Reduced efficacy of imipenem/cilastatin against A. baumannii was detected in aged mice. Vaccination of formalin-fixed A. baumannii provided 100% protection in young mice, whereas the efficacy of vaccine was completely diminished in aged mice. In conclusion, aging increased susceptibility to A. baumannii infection and impaired efficacies of antibiotics and vaccine. The aged mice model of A. baumannii pneumonia is a suitable model to study the effects of aging on A. baumannii infection and assess the efficacies of antibiotics and vaccines against A. baumannii for the elderly.
Objectives: Acinetobacter baumannii can cause severe nosocomial and community-acquired pneumonia.To study the pathogenesis of A. baumannii and to develop new treatments, appropriate mouse models are needed. Most reported mouse models of pulmonary A. baumannii infection are non-lethal or require mouse immunosuppression to enhance infection. These models are not suitable for studying host immune responses or evaluating immunotherapies. Methods: The virulence of 30 clinical isolates was assessed in mice. The most virulent isolate, SJZ24, was selected to develop a pneumonia model in immunocompetent mice. The cytokine mRNA expression in the lung was assessed with real-time PCR. The cell infiltration in bronchoalveolar lavage fluid (BALF) after SJZ24 infection was determined by flow cytometry. Vaccine efficacy was assessed using this model. Results: Intratracheal inoculation of SJZ24 (5 Â 10 7 CFU) resulted in death in 100% of the mice (5/5). SJZ24-infected mice showed high bacterial burdens in blood and organs as well as severe lung-tissue damage. Infection with SJZ24 induced increased inflammatory cytokine expression in the lung and increased neutrophil infiltration in BALF. Immunization with inactivated whole cells of SJZ24 showed 100% protection (5/5) against A. baumanni infection in this model. Conclusions: We established a lethal pneumonia model in immunocompetent mice with hypervirulent A. baumannii isolate SJZ24. This model can be used to study the immune response to A. baumannii infection and to evaluate vaccine efficacy.
Methicillin-resistant Staphylococcus aureus (MRSA) sepsis is a life-threatening medical condition thatMethicillin-resistant staphylococcus aureus (MRSA) sepsis is a blood infection with staphylococcus bacteria that are resistant to treatment with beta-lactam antibiotics. MRSA sepsis is a life-threatening medical condition that is caused by an overpowering immune response to MRSA infection and leads to systemic inflammation. Early diagnosis and rapid treatment increase the chances of patient survival, although the death rate from MRSA sepsis remains greater than 20% due to uncontrolled inflammation and drug resistance. These challenges necessitate investigations of new therapeutic approaches for MRSA sepsis.As an anti-inflammatory medication, dexamethasone has shown a beneficial effect on the adjunct therapies of experimental staphylococcal endophthalmitis 1,2 , septic arthritis 3 , septic endocarditis 4 , and septic nephritis 5 . Recent studies have also indicated that the clinical use of corticosteroids in sepsis can restore cardiovascular homeostasis 6 , terminate systemic and tissue inflammation 7 , restore organ function, and prevent death 8,9 .Recently, a series of investigations evaluated the therapeutic potential of such compounds in which a nitric oxide (NO)-releasing group was linked to well-established parent molecules 10,11 . NO-releasing glucocorticoid derivatives have shown an improved profile of pharmacological activity in terms of either enhanced anti-inflammatory efficacy or reduced side effects 12,13 . NO also represents an excellent antibacterial candidate because it is involved in the inhibition of bacterial respiration 14 and DNA replication 15,16 . NO has been shown to be capable of inducing the dispersal of MRSA biofilm  , which is considered a major virulence factor due to the protective exopolysaccharide matrix that is resistant to penetration by antibiotics 20 . Moreover, NO plays a critical role in the host innate immune response to various bacterial infections 21,22 . We hypothesized that NO-releasing
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