Intrapersonal mutation of rmpA and rmpA2: A reason for negative hypermucoviscosity phenotype and low virulence of rmpA-positive Klebsiella pneumoniae isolates

•Why are some rmpA-positive Klebsiella pneumoniae strains not hypermucoviscous?•K. pneumoniae isolates with preserved rmpA are hypermucoviscous and virulent.•Spontaneous frameshift mutation of rmpA and rmpA2 could lose the hypermucoviscosity phenotype and virulence in an isolate without c-rmpA.•A good functional rmpA, rmpA2 or c-rmpA is positively correlated with the hypermucoviscosity phenotype and virulence of K. pneumoniae.

Two Klebsiella pneumoniae isolates were simultaneously recovered from blood and urine cultures of the same patient. Both isolates were identical in genomic pulsotype by pulsed-field gel electrophoresis (PFGE). However, the hypermucoviscosity phenotype was confirmed in the blood strain but not the urine strain. A previously unrelated liver abscess K. pneumoniae hypermucoviscous isolate was used as a control. PCR, DNA cloning and sequencing for the plasmid-borne rmpA and rmpA2 genes and the chromosome-borne rmpA gene (c-rmpA) revealed negative c-rmpA with natural frame-shift mutation of rmpA and rmpA2 genes in the urine strain. The blood strain was negative for c-rmpA with rmpA2 mutation but no mutation in rmpA. The control strain was positive for c-rmpA with rmpA2 mutation but no mutation in rmpA and showed the highest virulence in mouse lethality experiments [median lethal dose (LD50) = 50 CFU], which was followed by the blood strain (LD50 = 2.47 × 103 CFU) and the urine strain (LD50 > 107 CFU). The control and blood strains were highly serum resistant, whereas the urine strain was sensitive to serum killing. In conclusion, intrapersonal concurrent mutation of rmpA and rmpA2 genes in the absence of c-rmpA could be a reason for the negative hypermucoviscosity phenotype and low virulence in rmpA-positive K. pneumoniae.