Rotating Magnetic Field Increases β-Lactam Antibiotic Susceptibility of Methicillin-Resistant Staphylococcus aureus Strains.

Marta Woroszyło,Daria Ciecholewska-Juśko,Marcin Wardach,Karol Fijałkowski,Daniel Styburski,Patrycja Szymczyk-Ziółkowska,Adam Junka,Radosław Drozd,Paweł Migdał

doi:10.3390/ijms222212397

Abstract

Methicillin-resistant strains of Staphylococcus aureus (MRSA) have developed resistance to most β-lactam antibiotics and have become a global health issue. In this work, we analyzed the impact of a rotating magnetic field (RMF) of well-defined and strictly controlled characteristics coupled with β-lactam antibiotics against a total of 28 methicillin-resistant and sensitive S. aureus strains. The results indicate that the application of RMF combined with β-lactam antibiotics correlated with favorable changes in growth inhibition zones or in minimal inhibitory concentrations of the antibiotics compared to controls unexposed to RMF. Fluorescence microscopy indicated a drop in the relative number of cells with intact cell walls after exposure to RMF. These findings were additionally supported by the use of SEM and TEM microscopy, which revealed morphological alterations of RMF-exposed cells manifested by change of shape, drop in cell wall density and cytoplasm condensation. The obtained results indicate that the originally limited impact of β-lactam antibiotics in MRSA is boosted by the disturbances caused by RMF in the bacterial cell walls. Taking into account the high clinical need for new therapeutic options, effective against MRSA, the data presented in this study have high developmental potential and could serve as a basis for new treatment options for MRSA infections.

Highlights

To investigate the above hypotheses we aimed to answer the following questions: is it possible to increase the susceptibility of Methicillin-resistant strains of Staphylococcus aureus (MRSA) strains towards β-lactam antibiotics in the presence of the rotating magnetic field (RMF)?; is the observed effect connected to the influence of the RMF on the antibiotic molecules, bacterial cells or both?; does the observed effect depend on the bacterial strain and apply to the entire group of β-lactams?; is the observed effect of a permanent character or it occurs only in the presence of the RMF? the associations between RMF parameters, as well as exposure conditions and the changes in antibiotic susceptibility, were analyzed
Our findings showed that an increase in antibiotic susceptibility in all RMF-exposed cultures was obtained for seven out of the eleven β-lactam antibiotics included in the experiment (Table 3, Figure 2, Supplementary Figure S4)
It is a type of stimulus unknown to the bacterial pathogens we challenged by its means

Summary

Introduction

Methicillin-resistant strains of Staphylococcus aureus (referred to as MRSA) have developed creativecommons.org/licenses/by/ 4.0/). Resistance to most β-lactam antibiotics including penicillins, cephalosporins (with the exception of ceftaroline and ceftobiprole) and carbapenems [1]. MRSA has been identified as the most common etiological factor of skin and soft tissue infections in United. It is believed that even ongoing development of new (other than β-lactam) antibiotics and advances in infection prevention will not prevent MRSA from remaining one of the most prominent pathogens with persistently high mortality [5]. The main reason behind the above-mentioned evolutionary success of this pathogen in the nosocomial and, in recent years, community environments, is the fact that MRSA harbors the mecA gene which codes alternative penicillin-binding protein, PBP2a, responsible for the resistance mechanism in question. The native PBP protein is the essential enzyme in the process of bacterial cell wall synthesis. β-lactam antibiotics, against which

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