is an opportunistic human pathogen that acquires nutrient metals from the vertebrate host amid infection. During zinc (Zn) scarcity, upregulates the expression of the predicted Zn metallochaperone, . Loss of compromises fitness during Zn deficiency, highlighting its role in this condition. To assess the contribution of ZigA to Zn-deficient , a multiparallel transposon sequencing and genetic interaction mapping approach was used. Transposon insertions in , encoding a predicted soluble lytic transglycosylase that tailors the bacterial cell wall, were enriched in the Zn-starved Δ transposon library. Based on previous studies as well as structural and sequence homology, we designated A1S_3027 as oluble ytic ransglycosylase (SltB). Further analyses revealed that inactivating rescued Δ fitness defects during Zn starvation. An ΔΔ mutant demonstrated altered cell envelope structures and increased cellular permeability, highlighting the roles of ZigA and SltB in maintaining cell envelope integrity. Furthermore, these mutants exhibited heightened resistance to β-lactam antibiotics and other cell wall-targeting agents. Alterations in cell envelope integrity in the ΔΔ mutant improved fitness in a murine pneumonia infection model, emphasizing the contribution of ZigA and SltB to pathogenesis. This study elucidates how functional interactions between ZigA and SltB modulate cell envelope integrity and pathogenesis of during Zn depletion. These findings reveal an interplay between metal homeostasis and cell envelope integrity, offering insights into how ZigA contributes to these critical cellular processes.