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      Recovering the susceptibility of antibiotic-resistant bacteria using photooxidative damage

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          Significance

          Bacteria resistant to antibiotics are now one of the great challenges for the control of infections. Many unsuccessful attempts have been made toward breaking such resistance through chemical modifications or addition of other conjugated compounds. This paper addresses the ability of photo-oxidation to reduce bacterial resistance, making them again sensitive to antibiotics, and explores relevant facts that may allow for the return of bacterial susceptibility to resistant organisms.

          Abstract

          Multidrug-resistant bacteria are one of the most serious threats to infection control. Few new antibiotics have been developed; however, the lack of an effective new mechanism of their action has worsened the situation. Photodynamic inactivation (PDI) can break antimicrobial resistance, since it potentiates the effect of antibiotics, and induces oxidative stress in microorganisms through the interaction of light with a photosensitizer. This paper addresses the application of PDI for increasing bacterial susceptibility to antibiotics and helping in bacterial persistence and virulence. The effect of photodynamic action on resistant bacteria collected from patients and bacteria cells with induced resistance in the laboratory was investigated. Staphylococcus aureus resistance breakdown levels for each antibiotic (amoxicillin, erythromycin, and gentamicin) from the photodynamic effect (10 µM curcumin, 10 J/cm 2) and its maintenance in descendant microorganisms were demonstrated within five cycles after PDI application. PDI showed an innovative feature for modifying the degree of bacterial sensitivity to antibiotics according to dosages, thus reducing resistance and persistence of microorganisms from standard and clinical strains. We hypothesize a reduction in the degree of antimicrobial resistance through photooxidative action combats antibiotic failures.

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          Most cited references41

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          Molecular mechanisms of antibiotic resistance.

          Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
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            Antibiotic resistance: a rundown of a global crisis

            The advent of multidrug resistance among pathogenic bacteria is imperiling the worth of antibiotics, which have previously transformed medical sciences. The crisis of antimicrobial resistance has been ascribed to the misuse of these agents and due to unavailability of newer drugs attributable to exigent regulatory requirements and reduced financial inducements. Comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms, resistance mechanisms, and antimicrobial agents. Multidisciplinary approaches are required across health care settings as well as environment and agriculture sectors. Progressive alternate approaches including probiotics, antibodies, and vaccines have shown promising results in trials that suggest the role of these alternatives as preventive or adjunct therapies in future.
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              Biofilms: Microbial Life on Surfaces

              Microorganisms attach to surfaces and develop biofilms. Biofilm-associated cells can be differentiated from their suspended counterparts by generation of an extracellular polymeric substance (EPS) matrix, reduced growth rates, and the up- and down- regulation of specific genes. Attachment is a complex process regulated by diverse characteristics of the growth medium, substratum, and cell surface. An established biofilm structure comprises microbial cells and EPS, has a defined architecture, and provides an optimal environment for the exchange of genetic material between cells. Cells may also communicate via quorum sensing, which may in turn affect biofilm processes such as detachment. Biofilms have great importance for public health because of their role in certain infectious diseases and importance in a variety of device-related infections. A greater understanding of biofilm processes should lead to novel, effective control strategies for biofilm control and a resulting improvement in patient management.
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                Author and article information

                Contributors
                Journal
                Proc Natl Acad Sci U S A
                Proc Natl Acad Sci U S A
                PNAS
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                0027-8424
                1091-6490
                20 September 2023
                26 September 2023
                20 September 2023
                : 120
                : 39
                : e2311667120
                Affiliations
                [1] aInstitute of Physics of São Carlos, University of São Paulo , São Carlos 13566-590, Brazil
                [2] bBiomedical Engineering, Texas A&M University , College Station, TX 77840
                Author notes
                1To whom correspondence may be addressed. Email: bagantovs@ 123456tamu.edu .

                Contributed by Vanderlei S. Bagnato; received July 10, 2023; accepted August 21, 2023; reviewed by Havva Funda Acar and Ron Allison

                Author information
                https://orcid.org/0000-0002-2978-7076
                https://orcid.org/0000-0002-4557-1013
                https://orcid.org/0000-0003-0361-9725
                https://orcid.org/0000-0003-4833-239X
                Article
                202311667
                10.1073/pnas.2311667120
                10523486
                37729197
                357305bd-3488-4717-97bc-75370ea0f1c8
                Copyright © 2023 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

                History
                : 10 July 2023
                : 21 August 2023
                Page count
                Pages: 7, Words: 4128
                Funding
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), FundRef 501100002322;
                Award ID: 001
                Award Recipient : Jennifer M Soares
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), FundRef 501100001807;
                Award ID: 2013/07276-1
                Award Recipient : Kate Cristina Blanco Award Recipient : Vanderlei S. Bagnato
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), FundRef 501100001807;
                Award ID: 2014/50857-8
                Award Recipient : Kate Cristina Blanco Award Recipient : Vanderlei S. Bagnato
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), FundRef 501100001807;
                Award ID: 2019/12694-3
                Award Recipient : Kate Cristina Blanco Award Recipient : Vanderlei S. Bagnato
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), FundRef 501100003593;
                Award ID: 465360/2014-9
                Award Recipient : Vanderlei S. Bagnato
                Categories
                research-article, Research Article
                microbio, Microbiology
                423
                Biological Sciences
                Microbiology

                photodynamic inactivation,antimicrobial resistance,staphylococcus aureus,antibiotic failures

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