(Sports Network) - Traveling across the country to face an NFC heavyweight probably isn't the best prescription after a second half collapse a week ago but that's the predicament the Buffalo Bills find themselves in as they prepare to visit the San Francisco 49ers.

The Bills will be attempting to rebound from their epic second-half collapse against New England last week. Buffalo squandered a 14-point lead by allowing the Patriots to score 45 second-half points in what turned about to be a 52-28 drubbing by New England.

The Bills allowed a mind-boggling 580 total yards, the second-highest total allowed in franchise history and the Pats scored touchdowns on six consecutive possessions.

Ryan Fitzpatrick registered 350 yards and four touchdown passes for Buffalo in the defeat but he was also picked off four times. Meanwhile, Bills running backs C.J. Spiller and Fred Jackson were limited to 33 and 29 yards, respectively, by New England's defense. Spiller suited up despite injuring his shoulder last week, while Jackson had missed the previous two games with a knee injury.

"Obviously, (the loss) showed us that we're not there yet," Fitzpatrick said. "To have that type of lead, we've got to be able to just continue to put the pressure on them."

The Niners, on the other hand, dismantled the New York Jets 34-0 last week, the team's first road shutout since their 2001 regular-season finale at New Orleans (38-0).

Carlos Rogers' 51-yard touchdown on a fumble return headlined a smothering defensive effort from the Niners in the blowout victory.

Frank Gore, Kendall Hunter and backup quarterback Colin Kaepernick all recorded rushing touchdowns as San Francisco bounced back strongly from a 24-13 upset loss at Minnesota in Week 3. Still, the story of the day belonged to the 49ers' defense.

San Francisco held the overmatched Jets to a paltry 145 yards and nine first downs while forcing four turnovers, including Rogers' recovery of a Santonio Holmes fumble that gave the Niners a 24-0 lead just seconds into the fourth quarter. The 49ers also blocked a punt that led to Hunter's one-yard touchdown plunge with 6:03 remaining.

"Anytime a defense comes out like that, it makes it easy on us," said 49ers quarterback Alex Smith.

The 49ers also registered three sacks of Mark Sanchez, who managed just 103 yards passing for New York, which was handed its most lopsided shutout loss since a 37-0 setback to Buffalo in the 1989 regular-season finale.

The all-time series between Buffalo and San Francisco is tied at five apiece and the two teams haven't met since Nov. 30, 2008 when the Niners edged the Bills, 10-3, in Western New York. The two teams haven't met in the Bay Area since Dec. 26, 2004, which was a 41-7 Buffalo rout.

WHAT TO WATCH FOR

San Francisco, which has won five straight home games against AFC opponents, has one of the NFL's best defenses and will attempt to press the turnover- prone Bills, who have dropped five consecutive on the road vs. NFC foes.

It all starts up front for the Niners, where versatile All-Pro Justin Smith generally overpowers opposing offensive lineman. That enables playmaking linebackers Patrick Willis and NaVorro Bowman to avoid the trash and make plays sideline to sideline. Meanwhile, Aldon Smith's pass rush figures to harass Fitzpatrick, who is prone to forcing things, and hard-hitting safeties Donte Whitner and Dashon Goldson are always around to pry the ball loose.

The Bills lead the NFL with 16 touchdowns this season and have impressive talent at the skill positions with Jackson, Spiller and receiver Stevie Johnson standing out. That said, it's hard to imagine a Buffalo offensive line short on talent holding up against the 49ers.

For Buffalo it's all about getting something out of their highly-paid but disappointing defensive line. If Mario Williams, Kyle Williams and Mark Anderson start living up to the hype, the Bills might be able to get something done against a San Francisco offense which lacks big play options on the outside.

The 49ers may get a boost in the backfield, however. Brandon Jacobs, the former New York Giant has been sidelined since suffering a knee injury in the second preseason game, could make his San Francisco debut Sunday.

"I'm ready to play," Jacobs told the 49ers' website Tuesday.

OVERALL ANALYSIS

The 49ers are playing with purpose and confidence, save for one hiccup in Minnesota. Buffalo, meanwhile, has to be questioning itself after its collapse against New England. Win or lose Bills coach Chan Gailey has a 24-hour rule, meaning you need to move on from your last game and focus on the upcoming opponent.

"It's one that will hang with us," Fitzpatrick said when talking about the loss to the Pats. "You try to block it out and you hope it doesn't linger into the next game."

Forgetting the Pats debacle is going to be a process for Gailey and it's unlikely his club bounces back and gets it done this week.

"I've got to work on the mind set of this football team and creating a sense of urgency every snap of every game," Gailey said.

Sports Network Predicted Outcome: 49ers 30, Bills 20

The Sports Network