Antibiotics and Innate Immunity: A Cooperative Effort Towards the Successful Treatment of Infections

Berti, Andrew D.; Rose, Warren E.; Nizet, Victor; Sakoulas, George

doi:10.1093/ofid/ofaa302

Cited by 22 publications

(18 citation statements)

References 38 publications

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“…Consistent with this, BSN14RB is uniquely able to survive in heparinated human blood compared to other isolates ( Fig 3E ). Host factors contribute significantly to the resolution of staphylococcal infection [ 44 ]. Staphylococci respond to the presence of neutrophils and defensins by modulating the classical SaeR-regulated production of virulence factors, paradoxically increasing pathogenicity by reducing immune recognition of cytotoxins [ 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Miller

Monk²,

Szubin³

et al. 2021

PLoS ONE

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Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.

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Section: Resultsmentioning

confidence: 99%

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Miller

Monk²,

Szubin³

et al. 2021

PLoS ONE

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“… 37 This includes the ability of antibiotics to affect virulence factors and other immune mechanisms that can modulate host response. 33 In a study by Volk et al, 38 it was discovered that the influence of antibiotic responses on the host immune system resulted in increased IL‐1 and lower IL‐10 production in patients with MRSA bacteremia treated with β‐lactam adjunctive therapy combined with standard antibiotics. Despite the failure of prior attempts to develop the S. aureus vaccine, emerging immunologic‐based therapies that combine virulence factor antibodies with standard therapeutics appear promising.…”

Section: Way Forward: Emerging Strategies For Tackling Antibiotic Res...mentioning

confidence: 99%

“…The exclusion of host immunology from antimicrobial pharmacology has undoubtedly resulted in an out‐of‐date understanding of antimicrobial therapy. Henceforward, the cooperation of antibiotics and the immune system should be objectively considered in the future, as this will hopefully evolve this field of science through the application of alternative media, host cytokine responses, and computer modeling 33 . Furthermore, there is a need to reconnect the understanding of innate immunity‐antibiotic relationships to improve treatments with antibiotics, slow bacterial resistance development, and uncover novel therapeutic approaches.…”

Section: Way Forward: Emerging Strategies For Tackling Antibiotic Res...mentioning

confidence: 99%

Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace

Nwobodo

Ugwu

Anie

et al. 2022

Clinical Laboratory Analysis

174

104

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Background Antibiotic resistance is currently the most serious global threat to the effective treatment of bacterial infections. Antibiotic resistance has been established to adversely affect both clinical and therapeutic outcomes, with consequences ranging from treatment failures and the need for expensive and safer alternative drugs to the cost of higher rates of morbidity and mortality, longer hospitalization, and high‐healthcare costs. The search for new antibiotics and other antimicrobials continues to be a pressing need in humanity's battle against bacterial infections. Antibiotic resistance appears inevitable, and there is a continuous lack of interest in investing in new antibiotic research by pharmaceutical industries. This review summarized some new strategies for tackling antibiotic resistance in bacteria. Methods To provide an overview of the recent research, we look at some new strategies for preventing resistance and/or reviving bacteria's susceptibility to already existing antibiotics. Results Substantial pieces of evidence suggest that antimicrobials interact with host immunity, leading to potent indirect effects that improve antibacterial activities and may result in more swift and complete bactericidal effects. A new class of antibiotics referred to as immuno‐antibiotics and the targeting of some biochemical resistance pathway components including inhibition of SOS response and hydrogen sulfide as biochemical underlying networks of bacteria can be considered as new emerging strategies to combat antibiotic resistance in bacteria. Conclusion This review highlighted and discussed immuno‐antibiotics and inhibition of SOS response and hydrogen sulfide as biochemical underlying networks of bacteria as new weapons against antibiotic resistance in bacteria.

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“…Antibiotic activities against bacterial pathogens have traditionally been considered only in terms of their direct killing effects (82). However, growing evidence indicates indirect effects of antibiotics through interaction with host innate immunity that can alter clinical outcomes (83)(84)(85). Yang et al identified antibiotic-induced host metabolic changes during infection and found that antibiotic treatment directly induced the host cells to produce metabolites that reduce drug efficacy and amplify phagocytic killing (86).…”

Section: Antibiotics Can Affect Host Immunity and Influence Clinical Outcomes Host Metabolic Changes Induced By Antibioticsmentioning

confidence: 99%

Section: Antibiotics Can Affect Host Immunity and Influence Clinical Outcomesmentioning

confidence: 99%

Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?

et al. 2021

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains a global health threat despite recent advances and insights into host-pathogen interactions and the identification of diverse pathways that may be novel therapeutic targets for TB treatment. In addition, the emergence and spread of multidrug-resistant Mtb strains led to a low success rate of TB treatments. Thus, novel strategies involving the host immune system that boost the effectiveness of existing antibiotics have been recently suggested to better control TB. However, the lack of comprehensive understanding of the immunomodulatory effects of anti-TB drugs, including first-line drugs and newly introduced antibiotics, on bystander and effector immune cells curtailed the development of effective therapeutic strategies to combat Mtb infection. In this review, we focus on the influence of host immune-mediated stresses, such as lysosomal activation, metabolic changes, oxidative stress, mitochondrial damage, and immune mediators, on the activities of anti-TB drugs. In addition, we discuss how anti-TB drugs facilitate the generation of Mtb populations that are resistant to host immune response or disrupt host immunity. Thus, further understanding the interplay between anti-TB drugs and host immune responses may enhance effective host antimicrobial activities and prevent Mtb tolerance to antibiotic and immune attacks. Finally, this review highlights novel adjunctive therapeutic approaches against Mtb infection for better disease outcomes, shorter treatment duration, and improved treatment efficacy based on reciprocal interactions between current TB antibiotics and host immune cells.

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Antibiotics and Innate Immunity: A Cooperative Effort Towards the Successful Treatment of Infections

Cited by 22 publications

References 38 publications

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace

Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?

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