Salmonella when it is phagocytosed and the fusion of the phagosome with the lysosome takes place, the low pH of the phagolysosome activates the PmrA/PmrB two component resistant mechanism that causes the induction of over 60 genes, 9 of which result in the synthesis of Lipid A that is in turn added to the nascent lipopolysaccharide component of the outer cell membrane. When this takes place, the organism is resistant to practically anything and it may replicate in situ. The killing of phagocytosed bacteria depends upon the retention of K+ within the phagolysosome which is used by vacuolar ATPases which hydrolyse ATP and the pH of the phagolysosome is reduced that needed for the activation of the zymogen granules into active hydrolytic enzymes that degrade the bacterium. Therefore, if you inhibit K+ efflux from the phagolysosome killing will take place. Phenothiazines such as thioridazine or chlorpromazine inhibit K+ transporters such as efflux pumps. It should be mentioned that the PmrA/PmrB component resistance system via activation of PmrD activates RamA which then promotes the cascade of genes that lead to the synthesis of the AcrB transporter of the AcrAB-TolC efflux pump. Hence, resistance of salmonella is now quite effective.
I recommend the following for more complete information.
1. Gunn JS. The Salmonella PmrAB regulon: lipopolysaccharide modifications,
antimicrobial peptide resistance and more. Trends Microbiol. 2008
10.1007/s10096-011-1435-3. Epub 2011 Oct 14. PubMed PMID: 21997771.
3. Spengler G, Rodrigues L, Martins A, Martins M, McCusker M, Cerca P, Machado L, Costa SS, Ntokou E, Couto I, Viveiros M, Fanning S, Molnar J, Amaral L. Genetic
response of Salmonella enterica serotype Enteritidis to thioridazine rendering
the organism resistant to the agent. Int J Antimicrob Agents. 2012
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4. Amaral L, Fanning S, Pagès JM. Efflux pumps of gram-negative bacteria: genetic
responses to stress and the modulation of their activity by pH, inhibitors, and
Most, if not all, Salmonella survive in macrophages. This is largely dependent on the SPI2 type 3 secretion system which inhibits intracellular trafficking and prevents fusion of phagosome and lysosomes. The ability to survive varies any may play a role in ability to cause systemic infection and host adaptation. But generally most Salmonella can survive in macrophages from most species if the SPI2 system is functional
Typhimurium survives well in macrophages. Well described in the murine typhoid model. Indeed these mechanisms are largely described first in it. There may be variation between isolates