28Elizabethkingia anophelis bacteria encounter fluxes of iron in the midgut of mosquitoes, 29where they live as symbionts. They also establish bacteremia with severe clinical 30 manifestations in humans, and live in water service lines in hospitals. In this study, we 31 investigated the global gene expression responses of E. anophelis to iron fluxes in the midgut 32 of female Anopheles stephensi mosquitoes fed sucrose or blood, and in iron-poor or iron-rich 33 culture conditions. Of 3,686 transcripts revealed by RNAseq technology, 218 were upregulated 34 while 112 were down-regulated under iron-poor conditions. Most of these differentially 35 expressed genes (DEGs) were enriched in functional groups assigned within "biological 36 process," "cell component" and "molecular function" categories. E. anophelis possessed 4 37 iron/heme acquisition systems. Hemolysin gene expression was significantly repressed when 38 cells were grown under iron-rich or high temperature (37℃) conditions. Furthermore, 39 hemolysin gene expression was down-regulated after a blood meal, indicating that E. anophelis 40 cells responded to excess iron and its associated physiological stress by limiting iron loading. 41By contrast, genes encoding respiratory chain proteins were up-regulated under iron-rich 42 conditions, allowing these iron-containing proteins to chelate intracellular free iron. In vivo 43 studies showed that growth of E. anophelis cells increased 3-fold in blood-fed mosquitoes over 44 those in sucrose-fed ones. Deletion of aerobactin synthesis genes led to impaired cell growth 45 in both iron-rich and iron-poor media. Mutants showed more susceptibility to H 2 O 2 toxicity 46 and less biofilm formation than did wild-type cells. Mosquitoes with E. anophelis 47 experimentally colonized in their guts produced more eggs than did those treated with 48 erythromycin or left unmanipulated, as controls. Results reveal that E. anophelis bacteria 49 respond to varying iron concentration in the mosquito gut, harvest iron while fending off iron-50 associated stress, contribute to lysis of red blood cells, and positively influence mosquito host 51 fecundity. 52