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Summary: Successful application of microorganisms to heavy metal remediation depends on their resistance to toxic metals. This study contrasted the differences of tolerant mechanisms between Pb2+ and Cd2+ in Enterobacter sp. Microbial respiration and production of formic acid showed that Enterobacter sp. had a higher tolerant concentration of Pb (>1000 mg l−1) than Cd (about 200 mg l−1). Additionally, SEM confirmed that most of Pb and Cd nanoparticles (NPs) were adsorbed onto cell membrane. The Cd stress, even at low concentration (50 mg l−1), significantly enlarged the sizes of cells. The cellular size raised from 0.4 × 1.0 to 0.9 × 1.6 μm on average, inducing a platelet‐like shape. In contrast, Pb cations did not stimulate such enlargement even up to 1000 mg l−1. Moreover, Cd NPs were adsorbed homogeneously by almost all the bacterial cells under TEM. However, only a few cells work as 'hot spots' on the sorption of Pb NPs. The heterogeneous sorption might result from a 'self‐sacrifice' mechanism, i.e., some cells at a special life stage contributed mostly to Pb sorption. This mechanism, together with the lower mobility of Pb cations, caused higher microbial tolerance and removal efficiency towards Pb2+. This study sheds evident contrasts of bacterial resistance to the two most common heavy metals. [ABSTRACT FROM AUTHOR]