Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut

Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if re-seeding-plasmid acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm cells re-seeding the gut lumen initiate clonal expansion. Extended spectrum beta-lactamase (ESBL) plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon re-seeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may be a limiting factor for reservoir formation in host tissues. Overall, our proof-of-principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time.

Synthesis of Oxygen-Rich Bismuth Oxybromide (Bi24O31Br10) Photocatalyst for High Efficiency Degradation of Sulfadiazine Under Simulated Sunlight

At present, compared with other antibiotic degradation systems, there are few literatures on pho- tocatalytic degradation of sulfadiazine (SDZ). In this research, it was firstly discovered that the oxygen-rich bismuth oxybromide (Bi24O31 Br10) photocatalyst can efficiently degrade SDZ under simulated sunlight. In this paper, the prepared Bi24O31Br10 photocatalyst by mixed solvothermal method represented outstanding photocatalytic performance. The catalyst synthesized at 120 °C and pH = 10 showed optimum degradation function in the samples prepared at various temperatures and pH value. After 3 h of irradiation, 96.2% of SDZ solution could be decomposed. The effects of preparation conditions, catalyst dosage, initial SDZ concentration and initial SDZ pH value on photocatalytic degradation efficiency were investigated systematically. Besides, the effect of active species was studied by trapping tests, and it was concluded that ‘O2 contributes the most to the photocatalytic process. A possible photocatalytic degradation mechanism was proposed.

Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities

Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still toxic. One explanation relies on the speed of detoxification, and another, non-exclusive explanation, relies on persistence, a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance to understand whether persistence is necessary to explain the survival of susceptible cells. Depending on the strain and experimental conditions, the decay of persister populations may follow an exponential or a power-law distribution. Therefore, we studied the impact of both distributions in the simulations. Moreover, we studied the impact of considering that persister cells have a mechanism to sense the presence of a toxic substance–a mechanism that would enable cells to leave the dormant state when the medium becomes nontoxic. The simulations show that surviving susceptible cells under indirect resistance may originate both from persister and non-persister populations if the density of detoxifying cells is high. However, persistence was necessary when the initial density of detoxifying cells was low, although persister cells remained in that dormancy state for just a few hours. Finally, the results of our simulations are consistent both with exponential and power-law decay of the persistence population. Whether indirect resistance involves persistence should impact antibiotic treatments.