Type IV Coupling Proteins as Potential Targets to Control the Dissemination of Antibiotic Resistance

Álvarez-Rodríguez, Itxaso; Arana, Lide; Ugarte‐Uribe, Begoña; Gómez-Rubio, Elena; Martín‐Santamaría, Sonsoles; Garbisu, Carlos; Alkorta, Itziar

doi:10.3389/fmolb.2020.00201

Cited by 24 publications

(18 citation statements)

References 126 publications

(231 reference statements)

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“…Continued structure–function studies of T4SSs also have important translational applications. One area of active investigation is in the design of small‐molecule inhibitors of T4SSs with the broad goals of suppressing dissemination of antibiotic resistance or mitigating virulence of clinically important pathogens (reviewed in Alvarez‐Rodriguez et al., 2020a; Boudaher and Shaffer, 2019). In some cases, inhibitors are being identified through high throughput screens for molecules blocking a T4SS‐mediated process, for example, conjugation (Cabezon et al., 2017; Casu et al., 2017; Shaffer et al., 2016).…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Type IV secretion systems: Advances in structure, function, and activation

Costa

Harb

Khara

et al. 2021

Molecular Microbiology

151

152

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Many bacterial species deploy Type IV Secretion Systems (T4SSs) to deliver DNA, protein, or other macromolecules to bacterial or eukaryotic cell targets (Li et al., 2019;Waksman, 2019). The T4SSs are composed mainly of two subfamilies, the conjugation systems and effector translocators (Cascales and Christie, 2003). Conjugation systems are of considerable medical concern for their roles in dissemination of mobile genetic elements (MGEs), often encoding resistance to heavy metals or antibiotics (Cabezon et al., 2015;Huddleston, 2014;Koraimann, 2018). The effector translocators mainly deliver proteins to eukaryotic target cells, although recent studies have also documented the interkingdom transfer of DNA,

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Section: Summary and Future Directionsmentioning

confidence: 99%

Type IV secretion systems: Advances in structure, function, and activation

Costa

Harb

Khara

et al. 2021

Molecular Microbiology

151

152

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“…Then, the relaxosome is recognized by cognate (or closely related) T4CP and targeted to the T4SS canal located in the donor cell envelope. The molecular basis of relaxosome recognition by the T4CP is not fully understood and has only been studied for a few model systems, as can be reviewed in [ 17 ]. Direct interactions between Mob (or DNA-Mob complex) and T4CP were reported (including RP4 TraG protein), suggesting the role of these interactions in relaxosome recognition [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, innovatory strategies for preventing CT-dependent AR spread have been proposed [ 12 ]. They rely on the use of specific inhibitors blocking each component of a CT system protein machinery [ 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular and Functional Characterization of MobK Protein—A Novel-Type Relaxase Involved in Mobilization for Conjugational Transfer of Klebsiella pneumoniae Plasmid pIGRK

Nowak

Sobolewska-Ruta

Jagiełło

et al. 2021

IJMS

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Conjugation, besides transformation and transduction, is one of the main mechanisms of horizontal transmission of genetic information among bacteria. Conjugational transfer, due to its essential role in shaping bacterial genomes and spreading of antibiotics resistance genes, has been widely studied for more than 70 years. However, new and intriguing facts concerning the molecular basis of this process are still being revealed. Most recently, a novel family of conjugative relaxases (Mob proteins) was distinguished. The characteristic feature of these proteins is that they are not related to any of Mobs described so far. Instead of this, they share significant similarity to tyrosine recombinases. In this study MobK—a tyrosine recombinase-like Mob protein, encoded by pIGRK cryptic plasmid from the Klebsiella pneumoniae clinical strain, was characterized. This study revealed that MobK is a site-specific nuclease and its relaxase activity is dependent on both a conserved catalytic tyrosine residue (Y179) that is characteristic of tyrosine recombinases and the presence of Mg2+ divalent cations. The pIGRK minimal origin of transfer sequence (oriT) was also characterized. This is one of the first reports presenting tyrosine recombinase-like conjugative relaxase protein. It also demonstrates that MobK is a convenient model for studying this new protein family.

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“…Bacterial conjugation is one of the main mechanisms by which bacteria can acquire antibiotic resistance genes through HGT [ 12 ]. Although these mechanisms are naturally occurring, the abuse of antibiotics has exercised an additional and continuous pressure that has increased horizontal gene transfer among bacteria, enhancing MDR bacteria selection [ 13 ].…”

Section: Antimicrobial Resistance Mechanismsmentioning

confidence: 99%

Incorporation of Antibiotics into Solid Lipid Nanoparticles: A Promising Approach to Reduce Antibiotic Resistance Emergence

2021

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Antimicrobial resistance is one of the biggest threats to global health as current antibiotics are becoming useless against resistant infectious pathogens. Consequently, new antimicrobial strategies are urgently required. Drug delivery systems represent a potential solution to improve current antibiotic properties and reverse resistance mechanisms. Among different drug delivery systems, solid lipid nanoparticles represent a highly interesting option as they offer many advantages for nontoxic targeted drug delivery. Several publications have demonstrated the capacity of SLNs to significantly improve antibiotic characteristics increasing treatment efficiency. In this review article, antibiotic-loaded solid lipid nanoparticle-related works are analyzed to summarize all information associated with applying these new formulations to tackle the antibiotic resistance problem. The main antimicrobial resistance mechanisms and relevant solid lipid nanoparticle characteristics are presented to later discuss the potential of these nanoparticles to improve current antibiotic treatment characteristics and overcome antimicrobial resistance mechanisms. Moreover, solid lipid nanoparticles also offer new possibilities for other antimicrobial agents that cannot be administrated as free drugs. The advantages and disadvantages of these new formulations are also discussed in this review. Finally, given the progress of the studies carried out to date, future directions are discussed.

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Type IV Coupling Proteins as Potential Targets to Control the Dissemination of Antibiotic Resistance

Cited by 24 publications

References 126 publications

Type IV secretion systems: Advances in structure, function, and activation

Type IV secretion systems: Advances in structure, function, and activation

Molecular and Functional Characterization of MobK Protein—A Novel-Type Relaxase Involved in Mobilization for Conjugational Transfer of Klebsiella pneumoniae Plasmid pIGRK

Incorporation of Antibiotics into Solid Lipid Nanoparticles: A Promising Approach to Reduce Antibiotic Resistance Emergence

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