Effect of mazEF, higBA and relBE toxin-antitoxin systems on antibiotic resistance in Pseudomonas aeruginosa and Staphylococcus isolates

Malawi Med J. 2018 Jun;30(2):67-72. doi: 10.4314/mmj.v30i2.3.


Background: A toxin-antitoxin (TA) system is a set of two or more closely linked genes that are encoded as a poison and a corresponding antidote on a protein. In typical bacterial physiology, an antitoxin binds to a toxin and neutralizes it, which prevents the bacterium from killing itself. We aimed to determine whether P.aeruginosa and Staphylococcus isolates have TA genes and to investigate whether there is a relationship between the expression levels of TA genes and resistance to antibiotics.

Methods: This study included 92 P. aeruginosa and 148 Staphylococcus isolates. RelBE, higBA genes were investigated in P.aeruginosa by multiplex polymerase chain reaction (PCR). The mazEF gene and the all TA genes expression were detected by real time PCR.

Results: RelBE and higBA genes were detected in 100% of P. aeruginosa. It was found that the level of relBE TA gene expression is increased in isolates sensitive to aztreonam compared to resistant isolates (p<0.05). The mazEF gene was detected in 89.1% of Staphylococcus isolates. In terms of MazEF gene expression level there was no significant difference between methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates (p>0.05) whereas there was a significant difference between MSSA and coagulase-negative Staphylococcus (CNS) isolates, MRSA and CNS isolates (p<0.05). The levels of mazEF gene expression were found to be higher in isolates sensitive to gentamicin, ciprofloxacin, levofloxacin, clindamycin, phosphomycine, nitrofurantoin, fusidic acid, cefoxitin compared to resistant isolates (p<0.05).

Conclusion: Studies on the prevalence and functionality of TA systems emphasize that it may be possible to have new sensitive regions in bacteria by activating TA systems. The results of this study lead to the idea that resistance to antibiotics can be reduced by increasing TA gene expression levels. But there is need for further studies to support and develop this issue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antitoxins / genetics*
  • Antitoxins / metabolism
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Drug Resistance, Microbial / genetics*
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / classification
  • Methicillin-Resistant Staphylococcus aureus / genetics*
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Microbial Sensitivity Tests
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / classification
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / isolation & purification
  • Pseudomonas aeruginosa / metabolism
  • Staphylococcal Infections / microbiology*
  • Toxin-Antitoxin Systems / genetics*


  • Anti-Bacterial Agents
  • Antitoxins
  • Bacterial Toxins