Methods: We performed whole-genome sequencing on 121 H. pylori clinical strains, among which 73 were metronidazole-resistant. Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed. Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H. pylori.
Results: Resistance due to RdxA truncation was identified in 34% of metronidazole-resistant strains. Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance. These sites included R16H/C in RdxA, D85N in the inner-membrane protein RclC (HP0565), V265I in a biotin carboxylase protein (HP0370) and A51V/T in a putative threonylcarbamoyl-AMP synthase (HP0918).
Conclusions: Our approach identified new potential mechanisms for metronidazole resistance in H. pylori that merit further investigation.
RESULTS: During 1980-2014, the FIs of NPK chemical fertilizers in China showed a significant growing trend. After reaching the highest value of 339 kg ha-1 in 2014, FIs were reduced to 303 kg ha-1 in 2019, higher than the 225 kg ha-1 maximum safe usage internationally recognized. Meanwhile, the pattern of change of FAE was one of 'decreasing to increasing', with values of 1 in 1980, 0.66 in 2003, and 0.80 in 2019. FIE basically showed an increasing trend, which could be divided into three stages: the first stage of low efficiency during 1980-2009, the second stage of medium efficiency after 2010, and the third stage of high efficiency after 2018.
CONCLUSION: From 1980 until 2019, a reduction of FAE from 1 to 0.80 with an average of 0.75 was observed in China. FIE was found between 0.65 and 0.85 and had the potential of upgrading by 15-35%. Therefore, China needs to improve the fertilizer use efficiency in order to strive for negative growth of chemical fertilizer intensity and ecological agriculture construction. © 2022 Society of Chemical Industry.