Differential Expression of the apsXRS System by Antimicrobial Peptide LL-37 in Commensal and Clinical Staphylococcus epidermidis Isolates

  • Sergio Martínez-García
  • Cipriano Chávez-Cabrera
  • Erika T. Quintana
  • Rodolfo Marsch-Moreno
  • Miguel A. Ibáñez-Hernández
  • Juan Carlos Zenteno
  • Marisa Cruz-Aguilar
  • Norma Velázquez-Guadarrama
  • Gabriel Betanzos-Cabrera
  • Sandra Rodríguez-Martínez
  • Mario E. Cancino-Diaz
  • Juan C. Cancino-DiazEmail author
Original research article


The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3–5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8–10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.


Staphylococcus epidermidis ApsXRS LL-37 Dlt MprF 



This work was supported by Secretaria de Investigación y Posgrado (SIP-IPN) Grant 20196630. M. Cancino-Diaz, S. Rodríguez-Martínez, and J.C. Cancino-Diaz acknowledges the COFAA-IPN and EDI-IPN and SNI-CONACyT fellowships.

Authors’ contributions

SMG and CCC performed the experiments and contributed at the same level. MR and MI performed the identification of lysyl-phosphatidylglycerol. JCZ and MCA carried out the determination of mutations. VN performed the determination of isolates with vancomycin-intermediate resistance. ETC, GBC, SRM and MECD helped with the conceiving of the study and the manuscript draft. JCCD conceived the study, purchased materials, and participated in the study’s design and coordination. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

This study was carried out in accordance with the recommendations of the ethics review board of the Escuela Nacional de Ciencias Biológicas-IPN with written informed consent from all subjects in accordance with the Declaration of Helsinki.


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Copyright information

© Association of Microbiologists of India 2019

Authors and Affiliations

  • Sergio Martínez-García
    • 1
  • Cipriano Chávez-Cabrera
    • 1
  • Erika T. Quintana
    • 1
  • Rodolfo Marsch-Moreno
    • 2
  • Miguel A. Ibáñez-Hernández
    • 3
  • Juan Carlos Zenteno
    • 4
  • Marisa Cruz-Aguilar
    • 4
  • Norma Velázquez-Guadarrama
    • 5
  • Gabriel Betanzos-Cabrera
    • 6
  • Sandra Rodríguez-Martínez
    • 7
  • Mario E. Cancino-Diaz
    • 7
  • Juan C. Cancino-Diaz
    • 1
    Email author
  1. 1.Department of MicrobiologyEscuela Nacional de Ciencias Biológicas, Instituto Politécnico NacionalMexico CityMexico
  2. 2.Department of Biotechnology and BioengineeringCinvestav-IPNMexico CityMexico
  3. 3.Department of BiochemistryEscuela Nacional de Ciencias Biológicas, Instituto Politécnico NacionalMexico CityMexico
  4. 4.Research UnitInstituto de Oftalmología Conde de ValencianaMexico CityMexico
  5. 5.Infectology LaboratoryHospital Infantil de México Federico GómezMexico CityMexico
  6. 6.Área Académica de Nutrición and Toxicología Clínica, Instituto de Ciencias de la SaludUniversidad Autónoma del Estado de HidalgoPachucaMexico
  7. 7.Department of ImmunologyEscuela Nacional de Ciencias Biológicas, Instituto Politécnico NacionalMexico CityMexico

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