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In this study, we found that four of the eight putative VapBC TA systems of\n                      <jats:italic toggle=\"yes\">Natrinema gari<\/jats:italic>\n                      J7-2 are functional in strain J7-2 and\n                      <jats:italic toggle=\"yes\">Haloferax volcanii<\/jats:italic>\n                      . Among them, the NgVapBC1 system is composed of the antitoxin NgVapB1 and the toxin NgVapC1, and the two proteins could form a NgVapBC1 complex. The NgVapBC1 system could be transcriptionally autoregulated, wherein a pseudo-palindromic sequence in the\n                      <jats:italic toggle=\"yes\">vapBC1<\/jats:italic>\n                      operon promoter acts as a negative\n                      <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                      -regulatory element, and the NgVapBC1 complex is a stronger repressor than NgVapB1. The qRT-PCR and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      toxicity analyses showed that strain J7-2 maintains a high\n                      <jats:italic toggle=\"yes\">vapB1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">vapC1<\/jats:italic>\n                      mRNA ratio through truncation of the\n                      <jats:italic toggle=\"yes\">vapBC1<\/jats:italic>\n                      operon transcript within the toxin-coding region for preventing the synthesis of excess toxin NgVapC1 to release toxicity abnormally. Mutational analyses showed that differential start codon usage by\n                      <jats:italic toggle=\"yes\">vapB1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">vapC1<\/jats:italic>\n                      and a \u22124 nt overlap of their stop and start codons contribute to maintaining a higher\n                      <jats:italic toggle=\"yes\">vapB1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">vapC1<\/jats:italic>\n                      mRNA ratio, and the \u22124 nt overlap-mediated translational coupling of\n                      <jats:italic toggle=\"yes\">vapB1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">vapC1<\/jats:italic>\n                      would enable both post-transcriptional and translational regulation of the NgVapBC1 system. The phenotypic comparison of strain J7-2 and its \u0394\n                      <jats:italic toggle=\"yes\">vapBC1<\/jats:italic>\n                      mutant revealed that the NgVapBC1 system contributes to population heterogeneity of decline-phase rather than exponential-phase strain J7-2 and facilitates the survival of subpopulations under stress conditions.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Although TA systems are regarded as versatile modulators of prokaryotic cell fate, their\n                        <jats:italic toggle=\"yes\">bona fide<\/jats:italic>\n                        physiological roles remain elusive. Moreover, so far, there is no report on the regulatory mechanism and function of haloarchaeal VapBCs, which constitute the major group of TA systems in haloarchaea. Our results demonstrate that a VapBC system of the haloarchaeon\n                        <jats:italic toggle=\"yes\">Natrinema gari<\/jats:italic>\n                        J7-2 is regulated at multiple levels and mediates the establishment of population heterogeneity, thereby facilitating the survival of the strain J7-2 population as a whole in diverse and changing environments. This study provides the first experimental evidence of the regulatory mechanism of the biological role of the VapBC system in conferring fitness advantages to haloarchaea.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.00747-26","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:00:45Z","timestamp":1784552445000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A haloarchaeal VapBC toxin-antitoxin system: regulatory mechanism and role in establishing population heterogeneity to facilitate survival of subpopulations under stress conditions"],"prefix":"10.1128","volume":"92","author":[{"given":"Dan","family":"He","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Hubei Key Laboratory of Cell Homeostasis, Wuhan 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