Can Methicillin-resistant Staphylococcus aureus Silently Travel From the Gut to the Wound and Cause Postoperative Infection? Modeling the “Trojan Horse Hypothesis”

Krezalek, Monika A.; Hyoju, Sanjiv; Zaborin, Alexander; Okafor, Ekenechukwu Emeka C.; Chandrasekar, Laxmi; Bindokas, Vitas; Guyton, Kristina; Montgomery, Christopher P.; Daum, Robert S.; Zaborina, Olga; Boyle-Vavra, Susan; Alverdy, John C.

doi:10.1097/sla.0000000000002173

Cited by 73 publications

(64 citation statements)

References 30 publications

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“…Trojan Horse 34 claimed a hypothesis trying to explain SSI pathogenesis, showing that pathogens remote from the SSI area -such as within the teeth, noses, or gastrointestinal tract -can be taken up by immune cells (macrophages or neutrophils) and travel to the wound site where they cause wound infections. This mechanism could be veri ed in a mice model, which can also explain why some infections occur latently following surgery and are due to organisms not found in the wound at the end of the operation 6,35 .…”

Section: Discussionmentioning

confidence: 99%

Nasal decolonization of Staphylococcus aureus and the risk of surgical site infection after surgery: a meta-analysis

Tang

Hui

et al. 2020

Preprint

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Aim: To assess the effects of nasal decontamination on preventing surgical site infections (SSIs) in people who are Staphylococcus aureus carriers undergoing different types of surgeries and diverse measures of decolonization. Methods: Relevant randomized controlled trials (RCTs) were identified through systematic searches of the PubMed, Embase, Web of science, and the Cochrane Library databases. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and the effects model was chosen according to the heterogeneity. Subgroup analyses were performed according to different types of surgeries and measures of decolonization that Staphylococcus aureus carriers were applied.Results: Twenty RCTs published between 1996 and 2019 involving 10526 patients were included. Pooled results showed that the overall SSIs and pulmonary surgery SSIs presented with a statistical difference in measures of nasal decontamination (RR=0.59 and 0.47, respectively, both p<0.01). However, the associations between nasal decolonization and increased risks of SSIs in orthopedics surgery or cardiovascular surgery remained insignificant in studies. As for the diverse measures of nasal decontamination, 50% used mupirocin, 15% used chlorhexidine, 30% used different types of antimicrobial drugs, and 5% use others. The SSIs rate were decreased after chlorhexidine (RR=0.474, 95% CI: 0.259-0.864), while no significant difference was shown in the use of mupirocin (RR=0.871, 95% CI: 0.544-1.394).Conclusion: It seems that nasal decolonization of Staphylococcus aureus may be associated with a reduction of SSIs in these patients, especially in patients who have been administered by pulmonary surgeries or treated with chlorhexidine.

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Section: Discussionmentioning

confidence: 99%

Nasal decolonization of Staphylococcus aureus and the risk of surgical site infection after surgery: a meta-analysis

Tang

Hui

et al. 2020

Preprint

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“…By raising the inoculum size to 2000 CFU/cm 2 , the infection rate could be increased up to 67% [ 121 ]. Taking into account the “Trojan horse” hypothesis, which relates to the ability of S. aureus to hijack circulating immune cells, such as neutrophils, to be able to travel to and infect other body sites, it becomes reasonable to assume that even a small initial number of bacteria might be just enough to establish an active focus of infection [ 122 , 123 , 124 , 125 ]. Hence, the evidently high number of bacteria that is used in conventional mouse models might obscure processes that are relevant to those early, low-bacterial burden stages of infection.…”

Section: Implications Of Staphylococcal Host Adaptation For Murinementioning

confidence: 99%

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Mrochen

Oliveira

Raafat

et al. 2020

IJMS

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Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future.

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“…Twenty-four hours after liver surgery, bacteria were detected in mesenteric lymph nodes (MLNs), whereas the liver remained sterile and exhibited optimal regeneration at 48 hours post-surgery ( Fig. 2b, c) (21,22). Since compartmentalization of intestinal microbiota in the gut lumen under homeostatic conditions depends on functional intestinal ILC3s (10,23), we investigated the impact of liver surgery on ILC3s and other immune cell populations.…”

Section: Major Liver Surgery Provokes Intestinal Microbial Translocatmentioning

confidence: 99%

Compartmentalization of intestinal bacteria by hepatic ILC3s prevents infections after surgery

Jakob

Sánchez-Taltavull

Yılmaz

et al. 2019

Preprint

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Infections after surgical interventions are assumed to be caused by contamination. We show by analyzing multicentric data of 6561 patients that surgical infections as well as sepsis had a predominantly enteric microbial signature irrespective of the type of surgery, suggesting failure of intestinal bacterial compartmentalization. In mice, we reveal that hepatic surgery induced dysregulation of intestinal and hepatic type 3 innate lymphoid cells (ILC3s) and intestinal leakage resulting in enteric bacterial translocation via lymphatic vessels. In the absence of hepatic ILC3s, inflammasome activation and the induction of antimicrobial peptide encoding genes, bacteria colonized remote systemic organs and impaired surgical outcomes. Conversely, mammalian-microbial commensalism is required for the education of host immunity to ensure optimal hepatic healing responses. In fact, microbial-derived products were sufficient for the induction of proliferative transcriptional networks in the mouse liver, as illustrated by serum transfer experiments, mass spectrometry and RNA expression analysis, indicating that the balanced exposure of the host to commensals is essential for recovery. This study reveals the intestinal origin of microbes causing complications after surgical interventions and highlights host protective mechanisms of controlled commensalism that prevent infections.

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Can Methicillin-resistant Staphylococcus aureus Silently Travel From the Gut to the Wound and Cause Postoperative Infection? Modeling the “Trojan Horse Hypothesis”

Abstract: Immune cells as Trojan horses carrying gut-derived MRSA may be a plausible mechanism of SSIs in the absence of direct contamination.

Cited by 73 publications

References 30 publications

Nasal decolonization of Staphylococcus aureus and the risk of surgical site infection after surgery: a meta-analysis

Nasal decolonization of Staphylococcus aureus and the risk of surgical site infection after surgery: a meta-analysis

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Compartmentalization of intestinal bacteria by hepatic ILC3s prevents infections after surgery

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