Antibiotic failure: Beyond antimicrobial resistance

de la Fuente-Nunez, Cesar; Cesaro, Angela; Hancock, Robert E.W.

doi:10.1016/j.drup.2023.101012

Cited by 25 publications

(10 citation statements)

References 116 publications

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“…Our findings revealed that most of the peptides tested displayed antimicrobial and immunomodulatory properties, thus providing a link between non-immune proteins and host immunity and supporting the "Meta Hypothesis". These results suggest that nonimmune proteins, whose functions are seemingly unrelated to host defense, may harbor peptides that contribute to immunological responses to invading pathogens, which are becoming increasingly prevalent 18,19 .…”

Section: Introductionmentioning

confidence: 98%

Peptides from non-immune proteins target infections through antimicrobial and immunomodulatory properties

Torres,

Cesaro,

de la Fuente-Nunez

2024

Preprint

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SummaryEncrypted peptides have been recently described as a new class of antimicrobial molecules. They have been proposed to play a role in host immunity and as alternatives to conventional antibiotics. Intriguingly, many of these peptides are found embedded in proteins unrelated to the immune system, suggesting that immunological responses may extend beyond traditional host immunity proteins. To test this idea, here we synthesized and tested representative peptides derived from non-immune proteins for their ability to exert antimicrobial and immunomodulatory properties. Our experiments revealed that most of the tested peptides from non-immune proteins, derived from structural proteins as well as proteins from the nervous and visual systems, displayed potentin vitroantimicrobial activity. These molecules killed bacterial pathogens by targeting their membrane, and those originating from the same region of the body exhibited synergistic effects when combined. Beyond their antimicrobial properties, nearly 90% of the peptides tested exhibited immunomodulatory effects, modulating inflammatory mediators such as IL-6, TNF-α, and MCP-1. Moreover, eight of the peptides identified, collagenin 3 and 4, zipperin-1 and 2, and immunosin-2, 3, 12, and 13, displayed anti-infective efficacy in two different preclinical mouse models, reducing bacterial infections by up to four orders of magnitude. Altogether, our results support the hypothesis that peptides from non-immune proteins may play a role in host immunity. These results potentially expand our notion of the immune system to include previously unrecognized proteins and peptides that may be activated upon infection to confer protection to the host.

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Section: Introductionmentioning

confidence: 98%

Peptides from non-immune proteins target infections through antimicrobial and immunomodulatory properties

Torres,

Cesaro,

de la Fuente-Nunez

2024

Preprint

Self Cite

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“…In this sense, the pharmaceutical industry has shifted its focus away from drugs intended for chronic use due to the resistance developed by microorganisms [6] . In this scenario, alternative therapies have surfaced as viable options for the management of bacterial infections [7] …”

Section: Introductionmentioning

confidence: 99%

Porphyrin−BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect

Pérez,

Durantini,

Martínez

et al. 2024

ChemBioChem

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A porphyrin‐BODIPY dyad (P‐BDP) was obtained through covalent bonding, featuring a two‐segment design comprising a light‐harvesting antenna system connected to an energy acceptor unit. The absorption spectrum of P‐BDP resulted from an overlap of the individual spectra of its constituent parts, with the fluorescence emission of the BODIPY unit experiencing significant quenching (96%) due to the presence of the porphyrin unit. Spectroscopic, computational, and redox investigations revealed a competition between photoinduced energy and electron transfer processes. The dyad demonstrated the capability to sensitize both singlet molecular oxygen and superoxide radical anions. Additionally, P‐BDP effectively induced the photooxidation of L‐tryptophan. In suspensions of Staphylococcus aureus cells, the dyad led to a reduction of over 3.5 log (99.99%) in cell survival following 30 min of irradiation with green light. Photodynamic inactivation caused by P‐BDP was also extended to the individual bacterium level, focusing on bacterial cells adhered to a surface. This dyad successfully achieved the total elimination of the bacteria upon 20 min of irradiation. Therefore, P‐BDP presents an interesting photosensitizing structure that takes advantage of the light‐harvesting antenna properties of the BODIPY unit combined with porphyrin, offering potential to enhance photoinactivation of bacteria.

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“…Chronic infectious diseases are often difficult to cure with a single treatment due to the nature of the causative pathogen continuously exists in the body, and long-term treatment may lead to the development of mutant strains resistant to the treatment. In fact, there are reports of the occurrence of multidrug-resistant pathogens in many chronic infectious diseases [ 2 3 4 ], which suggests the limitations of drug therapy in the treatment of chronic infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Current development of therapeutic vaccines for the treatment of chronic infectious diseases

Park,

Fatima,

et al. 2024

Clin Exp Vaccine Res

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Chronic infectious diseases refer to diseases that require a long period of time from onset to cure or death, the use of therapeutic vaccines has recently emerged to eradicate diseases. Currently, clinical research is underway to develop therapeutic vaccines for chronic infectious diseases based on various vaccine formulations, and the recent success of the messenger RNA vaccine platform and efforts to apply it to therapeutic vaccines are having a positive impact on conquering chronic infectious diseases. However, since research on the development of therapeutic vaccines is still relatively lacking compared to prophylactic vaccines, there is a need to focus more on the development of therapeutic vaccines to overcome threats to human health caused by chronic infectious diseases. In order to accelerate the development of therapeutic vaccines for chronic infectious diseases in the future, it is necessary to establish a clear concept of therapeutic vaccines suitable for the characteristics of each chronic infectious disease, as well as standardize vaccine effectiveness evaluation methods, secure standards/reference materials, and simplify the vaccine approval procedure.

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Antibiotic failure: Beyond antimicrobial resistance

Cited by 25 publications

References 116 publications

Peptides from non-immune proteins target infections through antimicrobial and immunomodulatory properties

Peptides from non-immune proteins target infections through antimicrobial and immunomodulatory properties

Porphyrin−BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect

Current development of therapeutic vaccines for the treatment of chronic infectious diseases

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