# The Complex Relationship between Virulence and Antibiotic Resistance
## 4 Regulation of Virulence and Antibiotic Resistance
### Post-Transcriptional Modifications  
Post-translational modifications are a well recognize mode of regulation; however, regulation of virulence and antibiotic resistance are also tied to post-transcriptional regulations. Post-transcriptional modifications, which act as a quality control mechanism to produce stable RNA transcripts, occur much more commonly in prokaryotes than is reported [152]. In _Salmonella enterica_ the translation of the virulence associated effector protein AvrA was completely abolished, while transcription was unaffected when the genes CsrA/CsrB were deleted. The expression of _avrA_ is regulated by a post transcriptional modification induced by the effective concentration of CsrA, which is achieved by sequestering of CsrB [153]. The post-transcriptional regulator Crc has been shown in recent research to modulate _P. aeruginosa_ antibiotic susceptibility and virulence. One study showed _crc_ deficient mutants of _P. aeruginosa_ were found to secrete lower levels of virulence factors, including toxins and proteins necessary for cytolysis; which is hypothesized to be the reason the mutant was also had reduced cytotoxicity in comparison to the wildtype strain. Lowered amounts of ToxA, virulence determinant exotoxin A, were also found in the vesicle-free secretome of _P. aeruginosa crc_ deficient mutant when compared to the wildtype [154]. _Mycobacterium tuberculosis_ is a significant health threat and the leading cause of death related to antimicrobial resistance. Recently, resistance to a potent pyrido-benzimidazole antimicrobial, 14, was investigated revealing that each mutation that conferred resistance fell in theputative DNA-binding and dimerization region of _rv2887_, a transcriptional repressor of the multiple antibiotic resistance regulator (MarR) family. The mutations in _rv2887_, led to increased expression of _rv0560c_, a methyltransferase that N-methylatedes 14 to abolish its activity [155]. Alternatively, since the production and use of bacterial virulence factors in _Yersinia_ spp. Is energetically costly, their expression is tightly regulated [156]. These post transcriptional methods involve binding of mRNA with a variety of molecules, including regulatory RNA-binding proteins such as YopD and the low calcium response secretion chaperone, small regulatory and non-coding RNAs such as Ysr35, thermosensors such as _yscW-Icf_ intergenic region, and RNases [156].  
While the presence of post-translational modifications has been shown to increase virulence factors, the lack of post-transcriptional modifications to rRNA has been shown to cause an increase in antibiotic resistance to some antibiotics. For example, the _tylA_ encodes a methyltransferase that methylates the 16S and 23S ribosomal RNA, however loss of methylation ability results in increased resistance to capreomycin and viomycin. On the other hand, post-transcriptional modifications have also been shown to increase susceptibility of a strain. Many post-transcriptional modifications are focused on the peptidyl transferase, which is the mode of action of many antibiotics. One study found that 8 genes in _E. coli_ involved in rRNA modification at the peptidyl transferase, when knocked out had increased the susceptibility of _E. coli_ to peptidyl transferase inhibiting antibiotics [157].